Ouabain--a link in the genesis of high blood pressure? Hypertension or high blood pressure is a risk factor that increases risk of myocardial infarction, renal failure or cerebral stroke. The pathogenesis of hypertension is due to a variety of causes, including inherited predisposition, dietary habits, especially salt intake, smoking, and also 'general lifestyle'. But for the scientist interested in the complex interplay of physiological and molecular factors, the actual causes of high blood pressure remain uninvestigated. The following article is concerned with new reports that ouabain, a plant derivative, occurs in human beings, in whom it appears to have a hormonal function; ouabain may even play a key role in the pathogenesis of hypertension. We are thus brought a step closer to the background of cardiovascular disease; we may also be afforded a lead to a new therapeutic principle.


Speed and consistency of human decisions to swallow or spit sweet and sour solutions. Measurements of the frequency and speed of spitting or swallowing citric acid, sodium saccharin, or mixture solutions, using the taste of one of them as the definition of what was to be spit, revealed that 'correct' spits occurred on > or = 70% of trials with equal reliability and latency among the liquids, indicating that recognition-based rejection decisions in adult humans are as rapid and consistent for an arbitrary sweet taste as for a sour or mixed taste.


Amiloride impairs the cholinergic regulation of potassium permeability in the human sweat gland but not in the rat submandibular gland. Potassium permeability was monitored in human sweat glands and rat submandibular glands. Acetylcholine increased permeability in both tissues and the responses consisted of transient, calcium-independent and sustained, calcium-dependent components. Amiloride, a drug which inhibits Na(+)-H+ countertransport, impaired the regulation of potassium permeability in sweat glands but not in the submandibular gland. It is suggested that the stimulus-permeability coupling process in the sweat gland may be sensitive to the lowering of internal pH.


Heterogeneous responses of canine basilar and middle cerebral arteries to serotonin at normal and high CO2 tension. The responses of basilar arteries (BAs) to serotonin were attenuated by high PCO2 (86 +/- 1 mm Hg) and the pH matched acidotic solution (PCO2 37 +/- 1 mm Hg), whereas the responses of middle cerebral arteries (MCAs) were not. High PCO2 decreased the basal tone of both arteries, and the changes in basal tone due to high PCO2 were not influenced by 3 x 10(-7) M imipramine, 10(-5) M pargyline or 10(-4) M aspirin. The responses of BAs to serotonin were attenuated by high PCO2 in the presence of imipramine, pargyline and aspirin. The responses of MCAs to serotonin were not influenced by high PCO2 in the presence of pargyline and aspirin, but attenuated by high PCO2 in the presence of imipramine.


Phosphocreatine and ATP concentrations increase during flow-stimulated metabolism in a non-contracting muscle. The gracilis muscle was excised from cold-acclimated rats, placed in vitro, and simultaneously perfused via its artery by high pO2 medium and superfused by low pO2 medium. With a doubling of the perfusion rate (from 50 to 100 microliters/min) phosphocreatine and ATP increased by 39% and 44%, respectively.


L-threo-3,4-dihydroxyphenylserine, a noradrenaline precursor, inhibits dopamine release and metabolism in the rat striatum in vivo. The effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on dopamine (DA) release and metabolism in the striatum was studied in freely moving rats by intracerebral microdialysis techniques. The DA level as well as the levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly decreased 140 min after the administration of L-threo-DOPS (50 mg/kg intraperitoneally). The results suggest that L-threo-DOPS inhibits the release and metabolism of DA in the striatum.


Piroxicam-induced analgesia: evidence for a central component which is not opioid mediated. Piroxicam is a nonsteroidal anti-inflammatory drug with a potent analgesic effect. In order to establish whether the analgesic action of Piroxicam has a central component, we studied the effect of the drug on the nociceptive orbicularis oculi reflexes evoked by electrical stimulation of the cornea and supraorbital nerve in healthy subjects. Piroxicam significantly suppressed the corneal reflex and R3 component of the blink reflex by 28% (p < 0.05) and 50% (p < 0.01), respectively. This effect was not reversed by the i.v. injection of naloxone. Beta-endorphin levels did not change. Piroxicam administration induces distinct inhibitory changes in nociceptive reflexes, which suggests that the analgesic action of the drug has a central component. The ineffectiveness of naloxone, and the lack of beta-endorphin changes, indicate that this central action is independent of the opioid system; other pain regulatory systems are probably involved.


Protection by chlorpromazine against lethality and renal toxicity of cisplatin in mice. The effect of chlorpromazine on acute lethal toxicity and nephrotoxicity induced by cisplatin was studied in mice. Chlorpromazine given (i.p.) 1 h before cisplatin greatly reduced lethal and renal toxicities of cisplatin. Chlorpromazine did not reduce the antitumor activity of cisplatin against Sarcoma 180 in ddY mice or EL-4 Leukemia in C57BL/6J mice.


Modulation of C2 and C3 gene expression of human peripheral blood monocytes by interleukin 1 beta, interferon gamma, tumor necrosis factor alpha and lipopolysaccharide. The effect of interleukin 1 beta (IL-1 beta), interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF alpha) and lipopolysaccharide (LPS) on the expression of the C2 and C3 genes in human adherent monocytes was studied. Stimulation of monocytes with IFN-gamma increased both C2 and C3 mRNA. IL-1 beta also increased C2 mRNA level, whereas C3 gene expression was not enhanced. TNF alpha failed to increase either C2 or C3 mRNA. LPS increased C2 mRNA, but suppressed C3 gene expression. These results suggest that C2 and C3 production by monocytes is regulated by IL-1 beta and IFN-gamma in the local tissues.


Replication of the heterogeneous heterochromatin of the sex chromosomes of Microtus cabrerae. We used bromosubstitution to investigate the mode of replication of different types of heterochromatin located in the sex chromosomes of Microtus cabrerae. Our results clearly show that, although the heterochromatin is late replicating, the replication timing of different types of constitutive heterochromatin is related to their banding properties: R-type heterochromatin replicates before G-type heterochromatin, and this replication is asynchronous in both sex chromosomes. Furthermore, the late replication behaviour of the inactive X may spread to its constitutive heterochromatin. In some cells, a region of the constitutive heterochromatin of the late replicating X spontaneously switches to early replication, which may be related to transcriptional activity. Replication behaviour of the constitutive heterochromatin in the Y chromosome is similar to that of the late replicating X.


Potentiation of antifungal activity of sesquiterpene dialdehydes against Candida albicans and two other fungi. The antifungal activity of two drimane sesquiterpene dialdehydes, polygodial (1) and warburganal (2), alone and in combination with several other substances, was examined against three fungi, Candida albicans, Saccharomyces cerevisiae and Pityrosporum ovale employing a broth dilution method. Anethole significantly synergized the activity of the two sesquiterpenoids against C. albicans and S. cerevisiae; however, it had only an additive effect against P. ovale. By contrast, two antioxidants, ascorbic acid (vitamin C) and BHA (butylated hydroxyanisole), noticeably enhanced the activity of the sesquiterpenoids against P. ovale, but had no effect against C. albicans and S. cerevisiae.


Biology of the hemopoietic microenvironment. In adult mammals, hemopoiesis takes place primarily in the bone marrow. The steady-state production of blood cells depends to a large extent on the interaction between hemopoietic stem/progenitor cells (HPC) and the different components of the microenvironment present in the medullary cavity. During the last three decades, in vivo and in vitro studies have allowed significant advances in understanding of the biology of such a hemopoietic microenvironment. Although not evident in histological sections, it is well known that the hemopoietic microenvironment is a highly organized structure that regulates the location and physiology of HPC. The hemopoietic microenvironment is composed of stromal cells (fibroblasts, macrophages, endothelial cells, adipocytes), accessory cells (T lymphocytes, monocytes), and their products (extracellular matrix and cytokines). Microenvironmental cells can regulate hemopoiesis by interacting directly (cell-to-cell contact) with HPC and/or by secreting regulatory molecules that influence, in a positive or negative manner, HPC growth. Recent in vitro studies suggest that functional abnormalities of the hemopoietic microenvironment may be implicated in the manifestation of certain hematological disorders such as aplastic anemia, and acute and chronic myelogenous leukemia. Thus, the characterization of the structure and function of the human hemopoietic microenvironment may have relevance in understanding and treating different hematological disorders.


Therapeutic effect of heme arginate in myelodysplastic syndromes. In order to investigate, whether heme would induce a response in myelodysplastic syndromes (MDS), 14 symptomatic patients (4 RA, 3 RARS and 7 RAEB) were treated with infusions of heme arginate 3 mg/kg body weight on 4 consecutive days, mostly for six cycles at 2-week intervals. Three of 14 patients (21%) showed an improvement in anemia (97-152, 79-120 and 92-114 g/l) within a few weeks, and 1 showed a milder increase in hemoglobin level (102-118 g/l). Of the 2 responders with marked thrombocytopenia, 1 showed an improvement in the platelet count (7-37 x 10(9)/l) and her regular need for red cell and platelet transfusions ceased. Some regression in bone marrow (BM) cytology was seen in all 3 responders. One of the responders is still in remission 41 months after cessation of the treatment, while in the other 2 the response lasted for 26 and 5 months. Four patients progressed during the treatment: 1 RA to RAEB, 1 RAEB to RAEBt and 2 RAEB, both with very complex chromosomal abnormalities at the beginning of the therapy, to acute erythroleukemia (AML-M6). Pretreatment delta-aminolevulinic acid synthase and heme synthase activities were generally low. Five patients had mild thrombophlebitis, but not after the infusion procedure was changed. No other side-effects common to growth factors occurred. In conclusion, it is likely that heme arginate has a therapeutic effect on some MDS patients, obviously by stimulating erythropoiesis. The response may be long-lasting.


Serum transferrin receptor in the megaloblastic anemia of cobalamin deficiency. In order to further study the relation between transferrin receptor and erythropoiesis we examined serum receptor levels in megaloblastic anemia, which is the classic example of ineffective erythropoiesis. We studied 33 patients with unequivocal cobalamin deficiency, only 22 of whom were anemic. High serum transferrin receptor levels were found in 12 patients, all of whom were anemic and had high lactate dehydrogenase (LDH) levels; in contrast, only 10 of the 21 patients with normal receptor levels were anemic. Receptor correlated most strongly with LDH (r = 0.573, p < 0.001) and, inversely, with hemoglobin values (r = -0.560, p < 0.001); it also correlated with ferritin and total bilirubin levels, but not with cobalamin, MCV or erythropoietin. No association was found with the hemolytic component of megaloblastic anemia, represented indirectly by haptoglobin levels. Changes induced by cobalamin therapy were also examined in 13 patients. Transferrin receptors rose in all 6 patients who initially had high levels and in 2 of 3 patients who had borderline levels, but not in the 4 patients with initially normal levels. The receptor levels began to rise within 1-3 days, peaked at about 2 weeks and returned to normal at about the 5th wk. The findings indicate that serum transferrin receptor levels reflect the severity of the megaloblastic anemia. The elevated receptor levels rise further with cobalamin therapy, however, as effective erythropoiesis replaces ineffective erythropoiesis, and these persist until the increased erythropoiesis returns to normal.


Red cell and plasma ferritin in a group of normal fetuses at different ages of gestation. Plasma and cell ferritin were determined in 47 normal fetuses at different gestational ages in order to evaluate fetal iron status. Plasma ferritin shows an increase during pregnancy (17.7 micrograms/l-mean geometrical value of fetuses between 18 and 20 weeks; 56.8 micrograms/l mean geometrical value of fetuses between 32 and 35 wk) and significantly correlates to hemoglobin and number of red blood cells. Red cell ferritin, too, increases throughout pregnancy (from 92.7 ag/cell to 265 ag/cell) and shows a better correlation to hemoglobin and number of red blood cells. Experimental evidence has been provided showing that the placenta takes up ferritin and is important in iron storage and transport (even against a concentration gradient). Our data support this theory and suggest a situation of positive balance between iron uptake and utilization during intrauterine life.


Validation of a serum-free growth factor-replenished in vitro culture system for hematopoietic progenitor cells in healthy donors and recipients of an allogeneic bone marrow graft. The in vitro colony formation of hematopoietic progenitor cells of bone marrow samples, taken before and early after allogeneic bone marrow transplantation (BMT), was investigated prospectively. In order to circumvent culture-related and sample-related variations, a serum-free recombinant growth factor-replenished culture system was developed using T cell- and monocyte-depleted bone marrow samples. Samples of healthy bone marrow donors were used to validate the technique. The standardized culturing technique gave reproducible results, with numbers of colonies above those in conventional conditioned-medium technique. Colony formation in vitro of myelomonocytic precursor cells was found decreased in graft recipients, also after addition of growth factors, in comparison with healthy donors. The growth-promoting effect of the combination of IL-3 + GM-CSF was superior to that of either growth factor alone or conditioned medium. No effect was observed of T lymphocytes and monocytes on in vitro colony formation after bone marrow transplantation, probably as a result of functional impairment of these cells at that period after transplantation.


A compendium of reviews in biochemistry and molecular biology published in the first half of 1992. 1. A compendium of reviews and mini-reviews in Biochemistry and Molecular Biology published in the first half of 1992 is presented. In all 499 titles are listed from 95 different publications. 2. This compendium presents the references by Journal Name. Keywords have been included with each reference to increase the value of the collection. Keyword and author cross-reference indexes are not included but are available in the electronic database from which this version was constructed. Should anyone wish to have this information in electronic form it can be distributed on MS-DOS formatted floppy disks in either Reference Manager or Medline format. The author should be contacted for details of the number of preformatted floppy disks required.


Regulation of transcription in eukaryotes by DNA-binding proteins. 1. The recognition of DNA by gene regulatory proteins is often mediated by structural motifs that comprise a protein DNA-binding domain. 2. Although binding of these proteins to DNA is not itself sufficient to affect transcription it is a necessary prerequisite. 3. This review summarizes recent studies that define structural motifs for DNA binding function of eukaryotic transcription factors.


Possible 110 kDa receptor for interleukin 2 in the chicken. Chicken lymphoblasts were generated from spleen cells which had been incubated with concanavalin A (Con A) for 48 h. Monoclonal antibodies (mAbs) were produced by immunizing mice with 48-h Con A lymphoblasts. These antibodies were used to identify chicken lymphokine receptors on Con A-activated lymphocytes. The cellular enzyme immunoassay (EIA), with lymphoblasts and spleen cells as the target cells, was used to select for specific mAbs. One mAb was found by EIA to have a strong response against the lymphoblasts but weak against resting spleen cells. By immunofluorescence staining, it reacted strongly with lymphoblasts and weakly with resting spleen, erythrocytes, and bursal cells. This mAb was also shown to inhibit the lymphokine activity present in conditioned medium that was collected from 24-h cultures of Con A-activated spleen cells. By immunoprecipitation, this mAb precipitated a lymphoblast surface antigen with a molecular weight of about 110 kDa. This receptor may be analogous to the putative interleukin 2 gamma subunit recently described in human and mouse cell lines.


Modification of proteins and other biological molecules by acetaldehyde: adduct structure and functional significance. 1. Chronic ethanol consumption is a major cause of liver disease. The modification of hepatic proteins by acetaldehyde (AcH), the primary metabolite of ethanol, has for some time been suggested as one of the major events initiating alcoholic liver disease. 2. These alterations in protein structure are believed to affect liver cell function, and may serve to activate the immune system. 3. This review considers the interaction between AcH and macromolecules and its functional implications.


Immune signalling at the maternal-fetal interface and trophoblast differentiation. In this review the afferent and efferent signals involved in immune signalling at the maternal-fetal interface are highlighted in the light of recent information. MHC antigen expression is reviewed. Immunizing mothers against class I and II MHC antigens can prevent spontaneous fetal resorption in mice. In addition, the CSF family of cytokines is not only secreted in placental tissues, but also play a role in trophoblast proliferation and differentiation. GM-CSF in particular appears to promote trophoblast syncytialization and the synthesis of human chorionic gonadotropin and human placental lactogen. Recent knock-out experiments indicate that CSF-1 is essential for complete fertility. Finally, the fact that the CSF cytokines promote HIV release from macrophages indicates that the knowledge gained in this area could lead to a better understanding of the transmission of the HIV virus from the mother to the fetus through the trophoblast.


Immunohistochemical studies on the distribution of lymphocytes in the peripheral and mucosal lymphoid tissues of laboratory musk shrews (Suncus murinus). We developed a new monoclonal antibody (mAb), named 1E9, which recognizes the immunoglobulin (Ig) M-like molecule of the insectivore laboratory animal, the suncus. This mAb was developed in order to investigate the distribution of surface Ig (sIg)-bearing lymphocytes in the lymphoid tissues of this animal. Immunohistochemically, the distribution of 1E9+ lymphocytes in the follicles of peripheral lymphoid tissues showed homology with such distribution in rodents. However, the lymphocytes in the follicles of the mucosal lymphoid tissues were not recognized by the mAb. These data suggest that from a comparative immunological viewpoint, our newly developed 1E9 mAb is useful for the characterization of sIg+ lymphocytes in the peripheral and mucosal lymphoid tissues of the suncus.


Reproducible proliferative responses of salamander (Ambystoma mexicanum) lymphocytes cultured with mitogens in serum-free medium. There are several reports that proliferative responses (tritiated thymidine incorporation (3HTdR)) of salamander splenocytes cultured with phytohemagglutinin-P (PHA) or concanavalin A (Con A) in 1% fetal bovine serum (FBS)-supplemented medium are either statistically insignificant or never approach the magnitude typically observed in similarly treated cultures of frog lymphocytes. The present study confirms these findings, but also reports highly significant and reproducible PHA-induced proliferation of axolotl splenocytes and thymocytes when the medium is supplemented with 0.25% bovine serum albumin (BSA) rather than 1% FBS. In one study, splenocytes from six of six axolotls cultured in BSA-supplemented medium displayed a dose-dependent response to PHA with stimulation indices (SLs) ranging from 4.2 to 14.1. In contrast, SLs of PHA-treated cells from the same animals, cultured in parallel in FBS-supplemented medium, ranged from 0.8 to 3.0. In a kinetic study (cells harvested from days 3-7), maximal proliferation in BSA-supplemented medium was noted after 5 days; cells cultured in parallel in FBS-containing medium were not responsive to the mitogen at any time point. Although axolotl splenocytes do not exhibit PHA-stimulated growth in FBS-supplemented medium, they are reproducibly stimulated in this serum-containing medium by phorbol 12-myristate, 13-acetate (PMA). This suggests that FBS may interfere with (or does not support) some early step(s) in lectin-induced signalling, rather than with proliferation itself.


Electrical-ionic control of gene expression. 1. Changes in turgor, in cell volume, in membrane potential, in intracellular ionic activities and, more recently, in spontaneous electrical activity have been reported to be causally linked to the expression of specific genes. 2. As a result, it has become clear that changes in membrane properties and/or in the intracellular "ionic environment" can play an important role in generating cell type specific physiological responses which indirectly--or maybe directly--affect gene expression. 3. Possible targets of the ionic "environment" are: the selective transport across biological membranes; the activity of certain (regulatory) enzymes; the conformation of some (regulatory) proteins; of chromatin; of the cytoskeleton; of the nuclear matrix; the association of the cytoskeleton with plasmamembrane proteins or RNA; the association chromatin-nuclear matrix; protein-DNA and protein-protein interactions etc. All these sites may be instrumental to "fine or coarse" tuning of gene expression. 4. The exact mechanisms by which changes in intracellular ionic environment are transduced, directly or indirectly, into alterations of the activity of trans-acting factors have not yet been fully uncovered. Changes in the degree of phosphorylation of regulatory proteins and/or of trans-acting factors may provoke fine tuning effects on cell type specific gene expression activity. 5. The intranuclear ionic environment is difficult to measure in an exact way. It can be influenced in a number of ways. The location of a gene, as determined by the position of the nucleus in the cytoplasm and by the association of chromatin to the nuclear matrix may be especially important in cells which can generate some type of intracellular gradient or in excitable cells. 6. In some somatic cell types--germinal vesicles may behave differently--the intranuclear inorganic ionic "environment" has been reported to be distinct from the cytoplasmic one. This challenges the widespread assumption that the nuclear envelope is always freely permeable to small molecules and inorganic ions. 7. It can be expected that the fast progress in the cloning of "electrically" controlled genes, in the identification of trans-acting factors, in their mode of interaction with genes and in the precise localization of genes within the nucleus may soon lead to substantial progress in this domain.


Immune system activation associated with a naturally occurring infection in Xenopus laevis. Immune system activation correlated with a naturally occurring infection has been found in the South African clawed frog Xenopus laevis. The microorganism thought to be the cause of this infection is coccobacilloid and approximately 1 micron in diameter. Since this microorganism does not grow on conventional bacterial media and it has been observed intracellularly, it may be an obligate intracellular bacterium. It has been found in Xenopus peripheral blood and in highly vascularized organs such as the spleen and liver. Splenomegaly is the only pathology thus far described for infected frogs; infection is not associated with increased morbidity or mortality. This infection has been found in all outbred frogs examined in shipments from one South African and three separate North American vendors, and has been transmitted to animals bred and raised in our laboratory. This infection has a profound effect on the immune system of Xenopus. Significant numbers of splenocytes from infected individuals exhibit morphology commonly associated with activated T lymphocytes. There is constitutive production of T-cell growth factor (TCGF) and both IgM and IgY. Freshly harvested splenocytes from infected animals proliferate in response to a TCGF-containing supernatant, indicating that they express receptors for TCGF, a trait exclusively exhibited by activated lymphocytes. These splenocytes also show an increase in the activation marker recognized by the monoclonal antibody FJ17.


Changes in the distribution of alpha beta and gamma delta T cells in blood and in lymph nodes from fetal and postnatal lambs. We have examined the distribution of alpha beta and gamma delta T cells, together with B cells, in a range of lymph nodes and blood before and after birth. The proportions of blood-borne alpha beta and gamma delta T cells changed markedly during development with a wave of increasing numbers of blood-borne gamma delta T cells occurring in the fetus during the last month of gestation and early postnatal life. gamma delta T cells constituted 18% of T cells in the blood of fetal lambs one month before birth and 60% of T cells in the blood of lambs one month after birth. There were also changes in the numbers of alpha beta T cells circulating through lymph nodes after birth. The proportion of CD4+ and CD8+ cells in mesenteric nodes increased substantially after birth, whereas that of gamma delta T cells decreased. Although B cells were present in much larger numbers in ileal lymph nodes in both the fetus and lamb, there was a large increase in the concentration of B cells in all lymph nodes in lambs after birth. In addition to the differences in the distribution of lymphocyte subsets circulating in fetal and postnatal lambs, markedly different growth patterns were also observed between lymph nodes before and after birth.


Mammalian small molecule methyltransferases: their structural and functional features. Structural and functional features of mammalian S-adenosyl-methionine-dependent small molecule methyltransferases are reviewed. The methyltransferases have similar protomer molecular weights in the range of 25,000-35,000. Two common sequence motifs are found in all enzymes of known sequence. Whereas the kinetic mechanisms may be different, the methyltransferases in the free form bind S-adenosylmethionine. Most, if not all, of mammalian small molecule methyltransferases appear to have vicinal thiols in a catalytically important area of the enzyme.


Trypsin digestion of arginase: evidence for a stable conformation manganese directed. 1. Controlled tryptic digestion of native arginase from rat liver suggests that Mn2+ promotes a stable conformation as shown by the following features. 2. An 18-fold increase in the half-life of arginase activity in the presence of Mn2+ is produced. 3. The stability of subunit B of arginase is increased in the presence of Mn2+ as revealed by SDS-PAGE during the time-course of trypsin cleavage. 4. The different digestion products of arginase with and without Mn2+ appearing during the time-course of tryptic treatment. 5. Different activity/bands protein ratio at any time of the tryptic digestion in the incubation mixtures, with and without Mn2+, are apparent.


Maternal alloimmunization in rat pregnancy: in vivo and in vitro studies of T-cell-dependent immunity to mating and third party alloantigens. Rat pregnancy, experimental pseudopregnancy, and experimental decidua induction promote skin allograft survival of paternal and unrelated skin donors by specific and nonspecific mechanisms. Experimental pseudopregnant females were given allogeneic cells by two routes: intraperitoneal (IP) and in utero (IU). The females injected by the IU route, with allosensitized spleen cells, tolerated paternal skin allografts (average 26 days) better than those from other experimental groups and even from allopregnant females bearing a paternal allograft. The orthotopic immunization by the IU route, as shown by an enhancing effect of in utero culture medium injection, seemed important. In vitro studies revealed that the ability of subscapular lymph node (SCLN) cells draining the allograft to destroy Wistar/Furth (W/Fu) target cells decreases markedly in parallel with prolongation of skin allograft survival. Suppression of lymphocyte-mediated cytotoxicity against W/Fu target cells exceeded 70% when SCLN cells were used as responder cells. We propose that maternal T-cell immunization (via in utero) against fetal antigens occurs in pregnancy and plays a role in maintaining fetal tolerance, while specific cell-mediated cytotoxicity is impaired. Both specific and nonspecific local factors may promote such an enhancement of allograft survival.


Analysis of the catalytic mechanism of juvenile hormone esterase by site-directed mutagenesis. 1. Juvenile hormone esterase (JHE) is a serine hydrolase selective for hydrolysis of the conjugated methyl esters of insect juvenile hormones. 2. We have investigated the mechanism of catalytic action of this enzyme by site-directed mutagenesis of the cloned enzyme and expression of the mutants in a baculovirus system. 3. A series of individual mutations of JHE were made to residues possibly involved in catalysis of juvenile hormones, and which are highly conserved in both esterases and lipases. 4. Mutation of the serine residue at position 201 to glycine (S201G), or aspartate 173 to asparagine (D173N), or histidine 446 to lysine (H446K), removed all detectable activity and these mutagenized enzymes were determined to be at least 10(6)-fold less active than wild type JHE. 5. Mutation of arginine 47 to histidine (R47H) decreased but did not abolish activity, with Km essentially unchanged at 66 nM for R47H compared to 34 nM for wild type JHE. 6. The kcat for R47H was decreased from 103 min-1 for wild type JHE to 1.9 min-1. 7. In addition, glutamate residue 332 was altered to glutamine (E332Q) and expressed in an Escherichia coli system. 8. This mutation was also found to remove all detectable activity. 9. From the results presented in this study and by comparison of JHE to other serine esterases and lipases, we predict that JHE possesses a Ser201-His446-Glu332 catalytic triad. 10. In addition, aspartate 173 and arginine 47 are essential for the efficient functioning of JHE.


Bovine proacrosin from cauda epididymal sperm: purification, characterization and partial sequencing at N-terminus. 1. In the present study, we isolated the two forms of proacrosin from acid extracts (pH 3.0) of cauda epididymal bovine spermatozoa by ammonium sulfate fractionation, gel filtration on Sephadex G-150 and affinity chromatography on Concanavalin A Sepharose 4B. The overall purification was 13-fold with respect to crude acid acrosomal extract. 2. The apparent molecular weight of the proacrosins determined by SDS-PAGE were 44,000 and 38,000. Both forms have proteinase activity on gelatin-SDS-polyacrylamide gel electrophoretic zymography. 3. The M(r) = 38,000 component was isolated by reverse phase HPLC. Thirty-nine amino acid residues at the N-terminus have about 72 and 77% sequence similarity with boar and human proacrosin, respectively. 4. The amino acid sequence of 14 amino acids at the N-terminus of the high molecular weight component (M(r) = 44,000) was determined after electroblotting on a polyvinylidene difluoride membrane. This portion of the molecule is identical with that of the low molecular weight component. 5. Proacrosin autoactivation followed the sigmoidal activation curve.


Effect of a sunflower oil-supplemented diet on protein kinase activities of rat liver plasma membranes. 1. The effect of a sunflower oil-enriched diet on plasma membrane-bound protein kinase C, protein kinase A, casein and tyrosine kinase activities was studied. 2. The diet induced an increase in the content of linoleic acid and a decrease in the content of palmitic acid. The anisotropy parameter (rs) of the fluorescence probe DPH and SDPH decreased strongly in the experimental group. 3. Protein kinase C was stimulated more than two times. Tyrosine kinase, protein kinase A and casein kinase activities were increased by 65, 57 and 40%, respectively. 4. We suggest that a more fluid lipid environment favours higher plasma membrane-bound protein kinase activities.


Mode of action of rabbit skeletal muscle cathepsin B towards myofibrillar proteins and the myofibrillar structure. 1. The mode of degradation of myofibrillar proteins and the structural changes in myofibrils due to the action of cathepsin B highly purified from rabbit skeletal muscle were studied. 2. Cathepsin B degraded myosin heavy chain, actin and troponin T, but not alpha-actinin, tropomyosin, troponin I or troponin C among myofibrillar proteins. 3. Cathepsin B optimally degraded myosin heavy chain, actin and troponin T at around pH 5. Degradation of myosin heavy chain produced 6 fragments, 180,000, 150,000, 87,000, 81,000, 75,000 and 69,000 Da, respectively. Actin was hydrolyzed into fragments of 41,000, 38,000 and 30,000 Da. Troponin T was degraded into fragments of 21,000, 12,000 and 10,000 Da. 4. Cathepsin B caused the fragmentation of myofibrils and disturbance of the lateral arrangement of myofibrils. 5. Cathepsin B partly disintegrated the Z-line and the M-line, and induced disordering of the arrangement of filaments in the I-band.


Identification of the classical androgen receptor in male rat liver and prostate cell plasma membranes. 1. Androgen-specific protein have been identified in cell plasma envelopes: gel filtration chromatography, Scatchard and steroid specificity spectrum analyses show the identity of the protein both from liver and ventral prostate plasma membranes (mol. wt 180,000) and nonidentity of the respective cytosol protein receptors. 2. The protein works only at physiological androgen concentration (0.14-14.0 nM of testosterone). 3. The protein possesses 2-orders higher androgen affinity than rat serum testosterone binding globulin (TeBG) and 1-order higher affinity compared to cytosol androgen receptor.


Impaired contraction and relaxation in aorta from streptozotocin-diabetic rats: role of polyol pathway. The effects of 3 months streptozotocin-induced diabetes mellitus on contraction and relaxation of aorta were examined in vitro. A further diabetic group was treated with a novel sulphonylnitromethane-based aldose reductase inhibitor for 3 months following diabetes induction. Diabetes resulted in reduced maximal tension production, particularly for responses to phenylephrine (p < 0.001) and serotonin (p < 0.001). However, with aldose reductase inhibitor treatment, responses were in the non-diabetic range. The ratio of maximum contractions to noradrenaline and phenylephrine were 28% elevated by diabetes (p < 0.01), which may suggest increased alpha 2-adrenoreceptor-mediated responses. Endothelium-independent relaxation to glyceryl trinitrate was unaffected by diabetes or treatment. By contrast, there were 38% deficits in endothelium-dependent relaxation to acetylcholine (p < 0.001) and Ca2+ ionophore A23187 (p < 0.001) with diabetes which were prevented by aldose reductase inhibitor treatment (p < 0.001). A 121% shift in the concentration giving a 50% maximum effect for acetylcholine towards lower sensitivity with diabetes (p < 0.001) was also largely corrected by treatment (p < 0.001). A non-diabetic group treated with aldose reductase inhibitor showed a 30% decrease in the 50% effective concentration for acetylcholine (p < 0.05). A 15% deficit in maximum relaxation to the ATP-sensitive K+ channel opener cromakalim for the diabetic group (p < 0.001) was prevented by aldose reductase inhibitor treatment (p < 0.01). We conclude that there are polyol pathway related abnormalities for contraction, some aspects of endothelium-independent relaxation, but particularly for endothelium-dependent relaxation in aorta from chronic streptozotocin-diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Oxygen radicals generated by the enzyme xanthine oxidase lyse rat pancreatic islet cells in vitro. The endothelium-associated enzyme xanthine oxidase is known to generate reactive oxygen intermediates which may damage the surrounding tissue. We investigated whether reactive oxygen intermediates released by xanthine oxidase exert a toxic effect on isolated rat islet cells. The xanthine oxidase (25 mU/ml)/hypoxanthine (0.5 mmol/l) system released reactive oxygen intermediates in vitro as detected by luminol in a chemiluminescence analysing system. The addition of nicotinamide inhibited the release of reactive oxygen intermediates in a dose-dependent manner (50% inhibition at 20 mmol/l). Exposure of islet cells to enzyme generated reactive oxygen intermediates caused lysis of 39% of the cells within 15 h. Monitoring the mitochondrial function of islet cells by the conversion of tetrazolium bromide to its formazan product revealed a significant reduction of the respiratory activity down to 51% of that of the controls by 30 min after the initiation of the xanthine oxidase reaction. Mitochondrial dysfunction preceded plasma membrane damage. The addition of nicotinamide, a radical scavenger and inhibitor of the DNA repair enzyme poly(ADP-ribose) synthetase protected the islet cells from lysis and partially preserved their mitochondrial activity in the presence of reactive oxygen intermediates. We conclude that activation of the endothelial enzyme xanthine oxidase, known to be induced by mediators of immune cells or by episodes of ischaemia and reperfusion causes islet cell damage with subsequent cell death in early phases of pancreatic islet cell destruction.


Effects of insulin on renal haemodynamics and the proximal and distal tubular sodium handling in healthy subjects. The effects of insulin on renal haemodynamics and renal sodium handling were studied in 10 healthy males. Using the euglycaemic insulin clamp technique, insulin was infused on separate days resulting in two levels of hyperinsulinaemia (41 +/- 3 and 90 +/- 7 mU/l, respectively). Renal haemodynamics and the proximal and distal tubular sodium handling were studied using inulin, para-amino-hippuric acid, sodium and lithium clearances. Low- and high-dose insulin infusions were followed by a fall in sodium clearance from 1.6 +/- 0.1 ml/min to 1.2 +/- 0.1 and 1.0 +/- 0.1 ml/min, respectively. Both levels of hyperinsulinaemia resulted in increased distal tubular sodium reabsorption. The distal antinatriuretic effect of insulin was associated with dose- and time-dependent decline in proximal tubular sodium reabsorption. The changes in proximal tubular sodium handling occurred without any significant changes in natriuretic factors, such as renal dopamine and plasma atrial natriuretic peptide levels. However, hyperinsulinaemia resulted in time- and dose-dependent increases in renal plasma flow, and renal vasodilatation could, possibly via changes in renal interstitial pressure, have contributed to the fall in the proximal tubular sodium reabsorption. The results also suggest that decreased proximal sodium reabsorption may be a compensatory mechanism counteracting the insulin-induced sodium retention.


A nationwide cross-sectional study of retinopathy and microalbuminuria in young Norwegian type 1 (insulin-dependent) diabetic patients. A nationwide cohort of Type 1 (insulin-dependent) diabetic patients was studied to determine the prevalence of retinopathy and microalbuminuria and to evaluate the association to various risk factors. Of 600 subjects with mean age of 19.8 years (range 8.0-30.3) and a mean duration of diabetes of 10.5 years (range 6.2-17.3), 371 (60%) volunteered for a clinical examination which included fundus photography, timed overnight urine samples for albumin excretion rate, measurement of arterial blood pressure and determination of HbA1c. Retinopathy was found in 122 of 371 patients (32.8%), in 3 of 41 (7.3%) patients aged less than 13 years. The youngest subject with retinopathy was 9.6 years old. Microalbuminuria was found in 44 of 351 patients (12.5%), in 1 of 41 (2.4%) patients aged less than 13 years. The youngest subject with microalbuminuria was 11.5 years old. Mean HbA1c was 8.6% (normal range 4.5-601%). Patients with retinopathy had significantly higher mean age (p = 0.0001), longer mean duration of diabetes (p = 0.0001), higher mean HbA1c (p = 0.009), and higher mean arterial blood pressure (p = 0.0001) compared to patients without retinopathy. In microalbuminuric patients HbA1c (p = 0.001) and mean arterial blood pressure (p = 0.01) were significantly higher compared to non-microalbuminuric patients, but there was no difference in age or diabetes duration. In a multiple logistic regression model, age, HbA1c, duration of diabetes and mean arterial blood pressure were found to be significantly associated with retinopathy, while HbA1c, mean arterial blood pressure and onset before 13.0 years of age were found to be associated with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)


Plasma apolipoprotein (a) is increased in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria. Patients with Type 2 (non-insulin-dependent) diabetes mellitus complicated by microalbuminuria or albuminuria, have an increased risk of developing macrovascular disease and of early mortality. Because lipoprotein abnormalities have been associated with diabetic nephropathy, this study tested the hypothesis that levels of apolipoprotein (a) are elevated in patients with Type 2 diabetes and increased levels of urinary albumin loss. Levels of apolipoprotein (a) in diabetic patients with microalbuminuria (n = 26, geometric mean 195 U/l, 95% confidence interval 117-324) and albuminuria (n = 19, 281 U/l, 165-479) were higher than in non-diabetic control subjects (n = 140, 107 U/l, 85-134, p < 0.05), and in the albuminuric group than diabetic patients without urinary albumin loss (n = 58, 114 U/l, 76-169, p < 0.05). Patients with microalbuminuria and albuminuria had levels comparable with patients undergoing elective coronary artery graft surgery (n = 40, 193 U/l, 126-298). Apolipoprotein (a) levels were higher in diabetic patients with macrovascular disease than in those without (n = 49, 209 U/l, 143-306 vs n = 54, 116 U/l, 78-173, p < 0.05). These preliminary results suggest that raised apolipoprotein (a) levels of Type 2 diabetic patients with microalbuminuria and albuminuria may contribute to their propensity to macrovascular disease and early mortality.


Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. We studied the cumulative incidence, concordance rate and heritability for diabetes mellitus in a nationwide cohort of 13,888 Finnish twin pairs of the same sex. The twins were born before 1958 and both co-twins were alive in 1967. Data on diabetes were derived through computerized record linkage from death certificates, the National Hospital Discharge Register and the National Drug Register. Records were reviewed in order to assign a diagnostic category to the 738 diabetic patients identified. Of these patients 109 had Type 1 (insulin-dependent) diabetes, 505 Type 2 (non-insulin-dependent) diabetes, 46 gestational diabetes, 24 secondary diabetes, 38 impaired glucose tolerance and 16 remained unclassified. The cumulative incidence of diabetes was 1.4% in men and 1.3% in women aged 28-59 years and 9.3% and 7.0% in men and women aged 60 years and over, respectively. The cumulative incidence did not differ between monozygotic and dizygotic twins. The concordance rate for Type 1 diabetes was higher among monozygotic (23% probandwise and 13% pairwise) than dizygotic twins (5% probandwise and 3% pairwise). The probandwise and pairwise concordance rates for Type 2 diabetes were 34% and 20% among monozygotic twins and 16% and 9% in dizygotic twins, respectively. Heritability for Type 1 diabetes was greater than that for Type 2 where both genetic and environmental effects seemed to play a significant role.


Predictive value of islet cell and insulin autoantibodies for type 1 (insulin-dependent) diabetes mellitus in a population-based study of newly-diagnosed diabetic and matched control children. Most studies evaluating immune markers for prediction of Type 1 (insulin-dependent) diabetes mellitus have focused on first degree relatives, although only 10% of newly-diagnosed patients have an affected first degree relative. The Swedish Childhood Diabetes Register identifies 99% of all diabetic children at diagnosis. In this population-based study, islet cell antibodies and insulin autoantibodies in 0-14-year-old Swedish consecutively-diagnosed patients and control subjects were analysed to define their sensitivity and specificity. Over 16 months (1986-1987), 515 Swedish children developed diabetes. Plasma samples were obtained from 494 (96%) patients, and 420 matched control children. Among patients, the frequency of islet cell antibodies was 84% (415 of 494), insulin autoantibodies 43% (145 of 334); 40% (135 of 334) were positive for both and 88% (294 of 334) were positive for one or both. Among control children, 3% (14 of 420) had islet cell antibodies, 1% (4 of 390) insulin autoantibodies, and 4% (16 of 390) had either autoantibody marker. The predictive value of finding a patient with the disease was only 7% since 4% of the control children were antibody-positive and the cumulative incidence rate up to 15 years of age is 0.38%. None of the autoantibody-positive (n = 21) or negative control children developed diabetes during 3 to 5 years of follow-up. Longitudinal investigations of islet cell or insulin-autoantibody-positive healthy children are necessary to accurately determine the conversion rate from marker positivity to disease onset.


Circadian variation of blood pressure in patients with diabetic nephropathy. The association between diurnal blood pressure variation and diabetic nephropathy was assessed in four groups of Type 1 (insulin-dependent) diabetic patients who underwent 24-h ambulatory blood pressure monitoring using an oscillometric technique. Patients with nephropathy, who had never been treated for hypertension (group D3, n = 13), were individually matched for age, sex and diabetes duration to a group of microalbuminuric patients (D2, n = 26), to normoalbuminuric patients (D1, n = 26) and to healthy control subjects (C, n = 26). Group D3 was also compared to patients with advanced nephropathy receiving treatment for hypertension, mainly a combination of angiotensin converting enzyme inhibitors, metoprolol and diuretics (D4, n = 11). In group D3 24-h diastolic blood pressure (85 +/- 8 mm Hg) was comparable to the results obtained in D4 (85 +/- 8 mm Hg) but significantly higher than in D2 (78 +/- 7 mm Hg), D1 (73 +/- 7 mm Hg) and C (73 +/- 7 mm Hg, p < 0.05, Tukey's test). The night/day ratio of diastolic blood pressure was higher in D3 (86 +/- 5%) and D2 (85 +/- 7%) than in C (80 +/- 7%, p < 0.02). This ratio was also elevated in group D4 (94 +/- 8%) compared to D3 (p < 0.05) corresponding to a marked smoothing of the diurnal blood pressure curve. The 24-h heart rate (beats per min) was significantly elevated in D3 (84 +/- 8) and D2 (80 +/- 10) compared with C (73 +/- 11, p < 0.05 Tukey's test), suggesting the presence of parasympathetic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of autoantibodies against islet amyloid polypeptide in human serum. Lack of association with type 1 (insulin-dependent) diabetes mellitus, or with conditions favouring amyloid deposition in islets. The Belgian Diabetes Registry. A radiobinding assay for the detection of autoantibodies against islet amyloid polypeptide was developed, analytically validated, and--in parallel with a similar assay for the detection of autoantibodies against insulin--applied to sera from recent-onset Type 1 (insulin-dependent) diabetic patients and from age- and sex-matched control subjects. There was no difference in islet amyloid polypeptide autoantibody titres between patient groups and matched control subjects, nor within subject groups according to age. At onset of Type 1 diabetes, elevated islet amyloid polypeptide-autoantibody levels (> 97th percentile of control subjects) were only detected in 1 of 30 patients aged 0-19 years and in 2 of 35 patients aged 20-39 years. By contrast, insulin autoantibodies were frequently demonstrated, in particular at onset of diabetes under age 20 (0-19 years: 18 of 30 patients; 20-39 years: 10 of 35 patients; p < 0.01 vs matched control subjects). Islet amyloid polypeptide autoantibodies were not detectable in 3 insulinoma patients nor in 37 patients (aged 33-70 years) with Type 2 diabetes (vs 1 of 40 in matched control subjects). In positive serum, adsorption onto protein A-Sepharose removed islet amyloid polypeptide binding activity, hereby confirming its antibody nature. In conclusion, Type 1 diabetes is associated with an age-dependent autoantibody reaction against insulin but not against islet amyloid polypeptide. Conditions associated with amyloid deposition in islets (Type 2 diabetes, insulinoma and ageing) do not favour the formation of autoantibodies against islet amyloid polypeptide.


On line continuous monitoring of subcutaneous tissue glucose in men by combining portable glucosensor with microdialysis. For the normalisation of blood glucose levels in diabetic patients by feedback controlled insulin delivery, a self-manageable and reliable method for continuous glucose estimation is still not available. By combining a commercially available needle type dialysis probe (molecular cutoff 20,000 Da) with a sensitive glucose sensor, we obtained a device for continuous glucose measurement in dialysate. This device was tested in healthy volunteers during a 75-g oral glucose tolerance test and in Type 2 (non-insulin-dependent) diabetic patients. Venous glucose and subcutaneous sensor signal were followed for 300 min (ten healthy subjects), 21 h (three healthy subjects) or 9 h (seven Type 2 diabetic patients). The recovery of the microdialysis was interindividually different, but after calibration, glucose levels in the dialysate and subcutaneous glucose sensor signal correlated well (r = 0.84-0.95). Under the assumption of a physiologic and technical delay between intravenous and subcutaneous glucose, correlation coefficient between intravenous glucose and subcutaneous sensor signal ranged from 0.60 to 0.93. We conclude that changes in blood glucose could be monitored in the subcutaneous tissue by the microdialysis technique in a continuous on line manner.


Early heart development in the chick embryo: effects of isotretinoin on cell proliferation, alpha-actin synthesis, and development of contractions. Isotretinoin is a potent retinoic acid used in the treatment of skin disorders. Though very effective, it is teratogenic if administered during pregnancy, and its teratogenic effect may be related to the normal activity of retinoids as signalling molecules in the embryo. Although its exact mechanism of action is unknown, it has been suggested that it causes its characteristic pattern of defects that includes heart defects, by inhibiting the migration of neural crest cells. However, other effects on cells are known. We studied early cardiac cell proliferation using incorporation of bromodeoxyuridine (BrdU) and detection with a monoclonal anti-BrdU. Proliferation in heart tissue of whole embryo cultures was inhibited in medium with 10(-6) M isotretinoin to 62% of the control level in myocardium. We studied its effects in culture on precardiac explant development in the absence of the neural crests. Culture of precardiac mesodermal-endodermal explants revealed that development of heart vesicles from the mesoderm was little affected, but the development of heartbeat was inhibited depending on dose in the 10(-5) to 10(-7) M range. The effect on development of contractions was augmented in the presence of serum; it could be duplicated by all-trans-retinoic acid, and it was reversible. Synthesis of the alpha-actin isotype, analyzed by isoelectric focusing, was found to be inhibited or delayed. The results suggest multiple effects of retinoids on growth, morphogenesis, and differentiation of early cardiac tissue, and are discussed in relation to the potential role of retinoids in early embryogenesis.


Gestation stage-specific frequency of adipogenic cells in Syrian hamster cell cultures. High frequencies (up to 50%) of spontaneous adipocyte differentiation are observed in cultures of 9 day gestation Syrian hamster embryos (E9 cells) within six to eight population doublings after primary culture. This is in contrast to the absence of adipogenic cells in primary cultures derived from later gestation age Syrian hamster tissue. In addition, E9 primary cultures contain a transient subpopulation of presumptive mesenchymal stem or progenitor cells that lack density dependent inhibition of growth [contact-insensitive (CS-) cells]. Analysis of the temporal pattern of expression of the CS- and adipocyte phenotypes during the proliferative life span of E9 cells demonstrates that maximal expression of the CS- phenotype precedes maximal expression of adipocyte differentiation. In addition, lipid accumulation appears to occur primarily, if not exclusively, in the contact-sensitive (CS+) cells that are derived from CS- cells. These observations suggest that primary E9 cultures contain either adipoblasts or primordial mesenchymal cells that become determined to the adipocyte lineage early during the in vitro life span of the cultures, and that the CS- phenotype may be a marker for these earlier developmental cell stages.


Genetic, cytogenetic and developmental analysis of the Drosophila melanogaster tumor suppressor gene lethal(2)tumorous imaginal discs (1(2)tid). Three of the twenty recessive-lethal tumor suppressor genes of Drosophila cause imaginal disc tumors in the homozygously mutated state. One of these is the lethal(2)tumorous imaginal discs (l(2)tid) gene. Histological preparations show the tumorous imaginal disc epithelium to consist of a mosaic of cells in monolayer and cells in clumped arrangement. In contrast, the wild-type imaginal disc epithelium is comprised exclusively of cells in monolayer arrangement. Mutant imaginal disc tissue pieces implanted into ready-to-pupariate wild-type larvae fail to differentiate. Implantation of l(2)tid imaginal disc tissue pieces in vivo into wild-type adult flies revealed a lethal, tumorous growth comparable to that in situ, thus characterizing the l(2)tid imaginal discs as truly malignant. The phenotypes of double mutants between two l(2)tid alleles and tumor suppressor genes, such as lethal(2)giant larvae and lethal(2)brain tumor, and the epithelial overgrowth mutant lethal(2)fat are described and discussed. Finally, we present the genetic, cytogenetic and molecular localization of the l(2)tid gene to the giant chromosome bands 59F4-6.


[Myocardial scintigraphy with Tc-99m-teboroxime: its feasibility and the evaluation of its diagnostic reliability. A comparison with thallium-201 and coronary angiography]. Tc-99m-teboroxime is a new tracer for myocardial perfusion scintigraphy. Its more remarkable features are the high myocardial extraction fraction, which is well correlated with the coronary blood flow, and the extremely rapid myocardial washout. This makes it necessary to complete the image collection shortly after the injection; on the other hand, repeated scans can be easily performed by renewed Tc-99m-teboroxime administrations. The aim of the present study was to test the feasibility of Tc-99m-teboroxime imaging and to evaluate its accuracy by comparing it with thallium-201 (TI-201) scintigraphy and coronary angiography. The patient population included 16 male patients (mean age 57.8 +/- 6.3 years) affected by suspect effort angina and/or with signs of exercise-induced ischemia; 12 of them had history of previous myocardial infarction. They underwent effort TI-201 and Tc-99m-teboroxime myocardial scintigraphy within 48 hours; left heart catheterization and coronary angiography were performed within 5 days. Scintigraphic images were collected in 3 planar views; each projection was divided in 3 segments, with the apical one shared by all views, for a total of 7 segments/study. Tracer uptake was qualitatively assessed and graduated according to a scoring scheme (from 0 = normal through 4 = absent uptake). Tc-99m-teboroxime scans could be accomplished without major problems in all subjects. The image quality was comparable to TI-201 in 8 patients and poorer in the remaining 8. Coronary angiography showed 50% obstructions in 15 patients; of them 1 subject had a normal scintigraphic pattern with both TI-201 and Tc-99m-teboroxime. The presence of previous infarction was recognized by both tracers in the 12 patients with infarct history. The number of abnormal segments and the uptake score were not significantly different in the Tc-99m-teboroxime rest and in the TI-201 redistribution images (segments: 2.8 +/- 1.4 vs 2.8 +/- 1.6; score: 5.6 +/- 4.2 vs 6 +/- 4.5). The diagnosis of effort ischemia was made in 13 patients with Tc-99m-teboroxime and in 12 patients with TI-201. The number of abnormal segments in the exercise Tc-99m-teboroxime and TI-201 myocardial scintigraphy was not significantly different (3.3 +/- 1.3 vs 3.3 +/- 1.5); on the contrary the defect score was significantly higher with Tc-99m-teboroxime than with TI-201 (9.5 +/- 4.3 vs 8.4 +/- 4.6, p < 0.03). Therefore the ischemic score (exercise defect score minus rest defect score) of Tc-99m-teboroxime was significantly higher than that of TI-201 (3.9 +/- 2.8 vs 2.4 +/- 2.2, p < 0.02). The two tracers gave comparable results in terms of recognition of patients with one-vessel or multi-vessel coronary artery disease. Planar myocardial scintigraphy with Tc-99m-teboroxime can be performed without major problems. In terms of clinical reliability the results are comparable to those of TI-201 scans. On the other hand, taking into account the poor image quality of Tc-99m-teboroxime scintigraphy, it is still impossible to predict its future role in the radionuclide imaging of coronary artery disease.


[Atrial natriuretic factor in patients with cardiac decompensation before and after chronic therapy with an angiotensin-converting enzyme inhibitor]. Patients with severe congestive heart failure often have high plasma Atrial Natriuretic Factor (ANF) and neurohormonal activation. Ace inhibitors give clinical and hemodynamic benefits and lower plasma angiotensin and norepinephrine levels. The interactions between ANF and the Ace inhibitors are mainly modulated via the renin angiotensin system. Plasma ANF, renin activity, urinary aldosterone and catecholamine levels were evaluated in 10 patients with congestive heart failure (at baseline, after 15 days of adequate treatment with digoxin and diuretics, and after 45 days of enalapril) in order to assess the changes of ANF and vasoconstrictor neurohormones with chronic Ace inhibitor therapy. ANF increased significantly in the congestive heart failure group compared to a normal subject control group (P < 0.001). After digoxin and diuretic therapy NHYA class improved significantly, but no significant hormonal changes were found. On the contrary, the addition of enalapril caused a significant decrease of plasma ANF and urinary aldosterone and catecholamines (P < 0.05). The relationship between the renin angiotensin system and catecholamines is complex but our findings indicate that: 1) Traditional therapy is effective in improving symptoms, but cannot induce a decrease of vasoconstrictive neurohormones; 2) ACE inhibitor therapy reduces ANF and neurohormonal activation. 3) ANF is a useful marker in evaluating the response to treatment.


[Ambulatory monitoring of left ventricular function: the assessment of transient episodes of ventricular dysfunction in patients with ischemic cardiopathy]. The recent development of an ambulatory radionuclide detector (VEST) to assess left ventricular (LV) function may enhance the detection of ischemia during routine daily activities in patients with coronary artery disease (CAD). The aim of this study was to evaluate the usefulness of VEST in monitoring LV ejection fraction (EF) responses to daily activities and sustained handgrip test (HG) in patients with CAD. 13 patients (12 men and 1 woman) with angiographically proven coronary artery disease were studied by VEST (mean 162 min, range 120 to 250 min). LV responses to different daily activities (walking and climbing stairs) and to HG were evaluated. Walking on a level surface and climbing stairs did not induce significant change in mean LVEF. However, a transient decrease in EF was observed in 4 (31%) and in 5 (38%) of the 13 patients during walking and climbing stairs, respectively. HG induced a significant (p < 0.01) reduction in mean EF. In particular, during HG, EF decreased > or = 5% in 11 (85%) of the 13 patients. A transient spontaneous decrease in LVEF lasting > or = 1 min was observed on 18 occasions in 11 patients with CAD; 5 episodes were symptomatic and 13 asymptomatic. ECG ST segment depression was recorded in 4 of the 5 symptomatic and in 5 of the 13 asymptomatic episodes. These results suggest that simultaneous monitoring of LV function and ECG may permit a better understanding of the incidence and severity of ischemic symptomatic and asymptomatic episodes.


[Valvular prolapse in autosomal dominant polycystic kidney]. The involvement of the cardiovascular system in hereditary connective tissue disorders has been known for a long time and produces abnormalities that usually affect valves and arterial walls. Valvular diseases in typical autosomal dominant illnesses such as polycystic kidney (PK) have recently been reported. To test the prevalence of valvular prolapses in this disease, we studied [with clinical, chest x-ray, electrocardiographic, and echocardiographic (monobidimensional and Doppler) examination] 21 subjects with PK (Group A) and 34 unaffected relatives (Group B). 36 subjects comparable in sex, age, blood pressure, body build and renal function, with other kinds of kidney diseases, were the control group (Group C). In group A, 7 subjects (33.3%) were found affected by mitral valve prolapse (MVP), of whom 3 also had mitral incompetence, 4 tricuspid valve prolapse and 2 aortic cusp prolapse with mild valvular insufficiency. Another 2 patients had evidence of mitral and aortic incompetence, respectively, without valvular prolapse, annulus ectasia or morphological features of a rheumatic valvular disease. In Group B, 8 subjects (23.5%) had MVP; In Group C, MVP was seen in only 1 patient (2.7%) and aortic incompetence in one other. Statistical analysis confirmed the significance of the greater prevalence of MVP in group A and B in comparison with group C (p < 0.01). The high prevalence of valvular abnormalities in autosomal dominant PK suggests a common genetic disorder producing a defect in the extracellular matrix. An alternative hypothesis is that of two discrete yet adjacent genes.


[Reference values for the echocardiographic calculation of left ventricular mass in normal children between the ages of 0 and 6]. Echocardiographic assessment of left ventricular mass (LVM) and mass/volume ratio (LVM/V) is an accurate method for evaluating left ventricular hypertrophy. However, reference values for LVM and left ventricular volume (V) in children under 6 years of age have not been well established. Therefore, we evaluated 106 consecutive children (60 males, 46 females, mean age +/- SD 35 +/- 28 months, range 0-72) free of cardiovascular disease by clinical, electrocardiographic and echocardiographic examination. LVM and V were determined by M-mode echocardiography. The 5th and 95th percentile values of LVM were: 7 and 21 grams for infants aged 0 to 6 months; 13 and 32 grams for 7 to 24 months; 23 and 41 grams for 25 to 36 months; 23 and 59 grams for 37 to 48 months; 30 and 60 grams for 49 and 60 months; 36 and 98 grams for 61 and 72 months. The 5th and 95th percentile values of V were: 4 and 20 ml for infants aged 0 to 6 months; 12 and 36 ml for 7 to 24 months; 16 and 43 ml for 25 to 36 months; 20 to 55 ml for 37 to 48 months; 27 to 64 ml for 49 to 60 months; 39 to 74 ml for 61 to 72 months. The 5th and 95th percentile values of M/V ranged between 1 and 2.3 for infants aged 0 to 6 months, and 0.7-1.2 for those aged 61 to 72 months. LVM, V and LVM/V were significantly (p < 0.0001) related to age, height, weight and body surface area, but were unrelated to gender.


[The differentiated effects of fibrinolysis on the coronary flow in patients with unstable angina]. Intracoronary (i.c.) thrombus is a frequent finding in patients (pts) with unstable angina (UA). Accordingly, thrombolytic treatment could be beneficial, as resolution of thrombus might result in increased delivery of blood flow to the ischemic regions. To test this hypothesis we studied 13 pts with UA refractory to maximal medical treatment and ST segment shift in the anterior leads. Coronary angiography was performed and great cardiac vein blood flow (GCVF; thermodilution) was measured in all pts within 48 hours (mean 29 +/- 13 hrs) from the last chest pain episode. Following angiography, pts received i.v. wrokinase (UK: 1 million IU/30 min); aortic pressure and GCVF were measured before and every 10 min during drug infusion, for a total time of 90 min. At baseline angiography 5/13 pts (Group 1) had evidence of i.c. thrombus (intraluminal filling defect or thrombotic subocclusion) in the ischemia-related left coronary artery, whereas 8 pts (Group 2) did not. Overall, coronary hemodynamics did not change significantly following drug administration: GCVF was 103 +/- 65 on baseline and 117 +/- 68 ml. min after UK; p > 0.05. Conversely, group analysis showed that UK increased GCVF and decreased anterior coronary resistances (mean aortic pressure/GCVF) in Group 1 (respectively from 86 +/- 33 to 114 +/- 41 ml. min: p < 0.005; and from 1.37 +/- 0.68 to 1.01 +/- 0.44 mmHg/ml. min: p < 0.05) but not in Group 2 (both: p > 0.05), despite similar effects on aortic pressure. Fibrinolytic treatment can be of therapeutic value in UA; UK has shown to increase regional coronary blood flow in selected pts presenting with refractory angina as well as evidence of i.c. thrombus at early angiography. Heterogeneity of angiographic findings could explain controversies in trials dealing with thrombolysis in UA.


[The contribution of pathology sections to the Italian Heart Transplant Project in the first 5 years of its activities (1985-1990)]. All the transplantation units within the Italian Heart Transplantation Project are supported by a section of pathology, devoted to the study of the recipient's heart, to patient monitoring by means of a schedule of endomyocardial biopsies, and, if that was the case, to examine the donor's heart and to analyse the causes of death. When successes and failures of the first five years of the Project's activity are weighed up, good results are observed: of the 847 operations performed (orthotopic, heterotopic and heart-lung transplants, and re-transplants) an actuarial survival rate of 77% at 5 years has been achieved. The sections of pathology believe to have contributed significantly to these results, examining as many as 10,446 endomyocardial biopsies. The indications for transplantation were: dilated cardiomyopathy (48.5%); ischemic (35.3%); valvular (5.9%) and congenital (2.4%) heart disease; hypertrophic cardiomyopathy (2.2%); endocardial fibroelastosis (1.7%); restrictive cardiomyopathy (1.4%); anthracycline cardiotoxicity (0.8%); myocarditis (0.8%); cardiac tumours (0.5%) and arrhythmogenic cardiomyopathy (0.2%). Distribution of recipients by sex and age varied according to the indications for transplantation: males were more common among the patients transplanted for ischemic (97%) and valvular (84%) heart disease, as well as for dilated (82%) and hypertrophic (78%) cardiomyopathy, whereas the opposite was true for endocardial fibroelastosis (males constituting 21%) and cardiac tumours (25%). Mean age at transplantation ranged from 49 years (ischemic heart disease) to 6 years (endocardial fibroelastosis). In the follow-up period, a 17.5% death rate was recorded; the main causes of death were the early failure of the transplanted heart (27 pts), postoperative complications (16), hyperacute rejection (4), acute rejection (18), infections (the singular most frequent cause of death, 35 pts), the proliferative endoarteritis of coronary branches (the so-called chronic rejection, that caused 21 deaths and required 14 re-transplants) and the development of neoplasms (11). The actuarial survival curve drops to 89% after the first postoperative month, abates to 82% at the end of the first year, and progressively decreases to 77% at the end of the fifth follow-up year. Rejection monitoring required an average number of 12.5 endomyocardial biopsies per recipient, and allowed 1.7 rejection episodes per patient to be diagnosed. The fewer were the rejection episodes occurring in a unit, the higher was the percentage of deaths due to infections.(ABSTRACT TRUNCATED AT 400 WORDS)


[The multiple coronary spasm as the cause of acute ischemic events. A case report of a simultaneous spasm of the anterior descending and the circumflex during coronary angiography]. A case of simultaneous coronary artery spasm during coronary arteriography is reported. The patient, a 48-year-old male smoker, with an important family history of sudden death, underwent coronary angiography 5 months after anterior myocardial infarction. There were no lesions in the coronary arteries at the angiographic study. At the end of the procedure there was a sudden contemporary spasm of the anterior descending and circumflex coronary arteries. This severe condition was resolved with intra-arterial nitroglycerin. The relevance of multicoronary spasm as a cause of acute ischemic events and the possible influence of family history are discussed.


[An aneurysm of the interatrial septum associated with Ebstein's anomaly: a case report]. Atrial septal aneurysm (ASA) is a known morphologic abnormality and has been largely investigated with two-dimensional echocardiography. Its association with other congenital or acquired diseases has also been described. However, the presence of ASA and concomitant Ebstein's anomaly in the same patient is a very unexpected finding in an adult subject. We therefore present the case of a young asymptomatic woman with this association.


[Rupture of the free wall of the left ventricle as the first manifestation of a myocardial infarct. A clinical case operated on with success]. A case of an undetected myocardial infarction in a patient with diabetes mellitus in which the first clinical sign was a syncope due to rupture of the left ventricular inferior wall is described. Survival was enhanced by a fast diagnosis (aided by the availability of an ECO 2D in the emergency room), by emergency pericardiocentesis with temporary haemodynamic stabilization and by prompt access to the Cardiosurgical Unit. A prompt diagnosis and treatment can allow the survival of patients, even in the extreme case that the ventricular wall rupture represents the first clinical manifestation of the myocardial infarction. The left ventricular free wall rupture in the course of myocardial infarction has a subacute pattern in about 30%, due to various mechanisms such as thrombosis or pericardial adherence over the ruptured wall.


[Aortocoronary bypass in a child with Kawasaki disease: the follow-up results]. The Kawasaki disease (mucocutaneous lymph node syndrome) usually affects children younger than 5 years, and is considered one of the most important causes of myocardial infarction in children. Some disagreement still exists regarding the following: the selection, surgery techniques, and follow-up outcomes of aortocoronary bypass grafting in Kawasaki disease. We describe the case of a three-year-old child with Kawasaki disease and with left and right multiple aneurysms, suffering from an antero-lateral myocardial infarction and inferior reinfarction. After thrombolytic treatment and coronary arteriography, left anterior descending aortocoronary bypass grafting was performed by using the autologous saphenous vein. After two years clinical, angiographic, ergometric and echocardiographic examinations show good surgical results with a global and regional kinesis improvement.


[The day-night changes in ambulatory blood pressure: another risk indicator in hypertension?]. In many different clinical situations, including some cases of secondary hypertension, nighttime blood pressure (BP) is abnormally increased in the majority of patients, with consequent flattening of the 24-hour BP profile, but the clinical importance of this finding in such conditions is unknown. In patients with essential hypertension, ambulatory BP has been shown to decrease by 10-20% from day to night, but in severe or malignant hypertension this diurnal BP rhythm may be blunted or even abolished. One of the reasons why the noninvasive monitoring of BP may be a reliable tool in assessing the day-night BP changes is the demonstration that frequent cuff inflations do not interfere to a significant extent with the haemodynamic effects of sleep. Part of the differences between the studies in the reported day-night BP drop may be artifactual, owing to the very different time intervals defining the daytime and nighttime subperiods in the single studies. In unselected patients with essential hypertension, a sizable proportion of subjects (17 to 40%) shows abnormally high nighttime BP, with consequent flattening of the 24-hour BP profile (the so called "non dippers", as opposed to the "dippers" who show a maintained diurnal BP rhythm). Several clinical studies carried out in independent laboratories show that the target organ damage induced by hypertension (left ventricular hypertrophy, cerebrovascular lesions) is more severe in hypertensive "non dippers" than in "dippers", possibly because of the different duration of exposure to high BP levels over the 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)


Minute non-polypoid adenoma of the colon detected by colonoscopy: correlation between endoscopic and histologic findings. To characterize the endoscopic features of minute non-polypoid neoplastic lesions of the colon, we investigated the endoscopic, macroscopic, and histologic findings in 34 lesions detected by colonoscopy, which were smaller than 5 mm and were endoscopically recognized as flat or depressed lesions. The lesions were divided into two groups according to their endoscopic features; 8 lesions were completely flat and the remaining 26 lesions were flat-topped elevations with a central depression. Macroscopic examinations revealed that the center of the endoscopically flat lesion was slightly elevated, whereas the center of the flat-topped elevation was characterized by a central depression. All of the lesions were histologically diagnosed as tubular adenomas. The flat lesions were composed of flatly elevated adenomatous glands, while the flat-topped elevations with a depression were characterized by surrounding hyperplasia arising from normal glands. The whole thickness of the mucosa was replaced by adenomatous glands in the lesions with an obvious central depression, while the adenomas tended to spread superficially in the lesions with a shallow depression. These findings suggest that pre-cancerous lesions other than small polyps do exist in the colon and that colonoscopic examination provides some clue toward a prediction of the histologic architecture of the lesions.


Diazepam versus midazolam for colonoscopy: a prospective evaluation of predicted versus actual dosing requirements. We performed a prospective, randomized, double-blind study to evaluate the efficacy of the currently recommended low doses of midazolam for conscious sedation compared with diazepam for colonoscopy. Each agent was administered in a fixed ratio dose in combination with meperidine, and titrated incrementally to allow for adequate sedation prior to initiating and during the procedure. The currently recommended starting dose of midazolam (0.03 mg/kg) proved to be very appropriate for pre-medication. In contrast, the currently recommended starting dose of diazepam (0.10 mg/kg) proved excessive in 21% of patients (especially in those aged > 65). The low initial and incremental doses of midazolam compared favorably with diazepam in all efficacy parameters studied and exceeded diazepam in post-procedure amnesia scores (p = 0.01). Moreover, the sedative effects of midazolam at these lower doses were not lost despite long duration procedures (> 40 min). We conclude that midazolam, given in small incremental doses, in combination with meperidine, produces effective conscious sedation for colonoscopy and exceeds diazepam in its amnestic effect.


Endoscopic classification of esophageal cancer: correlation with the T stage. Staging of esophageal squamous cell carcinoma is a prerequisite to assessing prognosis and deciding on appropriate treatment. Endoscopy provides one means of predicting the extent of tumor growth. Using the classification of the Japanese Society for Esophageal Diseases, which differentiates superficial (type 0) from more advanced stages of esophageal carcinoma, we studied 273 patients with squamous cell cancer of the esophagus. Histopathologic examination of resected specimens (N = 81) or endosonography (N = 128) served to correlate the endoscopically defined categories with the otherwise determined T stages. Not classifiable by endoscopy were 64 patients (23.4%), 42 of whom were pre-treated by means of chemo- or radiation therapy. In the remaining 209 patients, it could be shown that endoscopic assessment was both sensitive (78%) and specific (93%) in predicting the local extent of tumor (overall accuracy, 89%). Detailed analysis showed good sensitivity for stage 0 (83%) which corresponds to T-1 carcinoma and for stages 3 and 4 (82% and 83%) which represent T-3 and T-4 tumors. Only in endoscopic stages 1 and 2 was the concordance with the T stage (T-2) weaker, with a sensitivity of 52%. We conclude that prediction of local tumor extent by endoscopic observation is a generally reliable means of pre-operative staging esophageal cancer.


Evaluation of endoscopic ultrasonography in the pre-operative staging of carcinoma of the ampulla of Vater and common bile duct. Endoscopic ultrasonography (EUS) was performed in 23 patients with carcinoma of the ampulla of Vater (ampulla) and in 16 patients with common bile duct (CBD) carcinoma. These patients all underwent surgery. The layered structures of the duodenum, ampulla, and CBD, and the pancreas, portal vein, and regional lymph nodes were clearly identified by EUS using a transduodenal approach. With this technique, ampullary carcinoma appeared as a hypoechoic mass in 22 of 23 patients, and the 1 remaining cancer was not detected because of its small size. Carcinoma of the CBD also appeared as a hypoechoic mass in 12 of 16 patients. However, the remaining four appeared as hyperechoic masses. For these tumors, EUS had a high tumor detection rate (96 to 100%). In this regard, EUS was comparable to ERCP and was better than ultrasonography (US), CT, and angiography. Using EUS, we were also able to stage the extent of these tumors according to the involvement of the duodenal or CBD walls, invasion of the pancreas and portal vein, and spread to regional lymph nodes. The accuracy rates of cancer extent by EUS were 78% for ampullary carcinoma and 81% for CBD carcinoma when compared with surgical findings. We conclude that EUS is a valuable method for the detection and staging of tumors of the ampulla and CBD.


Age, anemia, and obesity-associated oxygen desaturation during upper gastrointestinal endoscopy. Although upper gastrointestinal endoscopy is generally a safe procedure, it is known to be associated with arterial oxygen desaturation. We studied 82 patients undergoing diagnostic upper gastrointestinal endoscopy following a standard premedication consisting of xylocaine throat spray and intravenous midazolam. The mean duration of endoscopy was 8.5 +/- 0.42 min and the mean dose of midazolam was 6.3 +/- 0.15 mg. The baseline SaO2 was 94.91 +/- 0.27% and it decreased after pre-medication to 92.84 +/- 0.40% (p < 0.001) and after intubation to 91.21 +/- 0.40% (p < 0.001). A fall greater than 4% saturation occurred for 15.68% of the total endoscopy time. SaO2 < 90% was seen for 16.7% and SaO2 < 85% occurred for 2.33% total endoscopy time. In patients > 65 years old, hemoglobin < 10 g/dl, or body mass index > 28, the baseline saturation was significantly lower and a reduced SaO2 was seen throughout the procedure. We identify old age, anemia, and obesity as independent risk factors for arterial oxygen desaturation. We recommend continuous monitoring before sedation, and giving supplemental oxygen to patients with these risk factors from the outset of upper gastrointestinal endoscopy.


Fentanyl for sedation during upper gastrointestinal endoscopy. The effects of sedation by intravenous fentanyl on the rate-pressure product (pulse rate x systolic blood pressure/100), arterial oxygen saturation, electrocardiographic change, and serum cortisol concentration were studied during gastroduodenoscopy in 84 patients randomized to receive fentanyl or no intravenous sedative (controls). Fentanyl administration increased the tolerance of patients and attenuated the endoscopy-induced rise in rate-pressure product and serum cortisol concentration. Desaturation of arterial oxygen was minimal and there was no difference in arterial oxygen saturation between the fentanyl group and the control group. Therefore, fentanyl appears to be a favorable sedative for upper gastrointestinal endoscopy, since its administration increased the tolerance of patients and decreased cardiac oxygen consumption.


Quality of air contrast barium enema performed the same day as incomplete colonoscopy with air insufflation. The quality of 17 air contrast barium enemas performed the same day as incomplete colonoscopies using air insufflation was compared with 21 air contrast barium enemas performed on a different day from incomplete colonoscopies. A gastrointestinal radiologist blinded to the timing of the procedures reviewed the barium studies scoring them as 1 (unsatisfactory) to 4 (excellent) in four areas. The mean overall quality score for the air contrast barium enemas done the same day as incomplete colonoscopy was 3.29 vs. 2.97 for those done on a different day (p = 0.24). There were no significant differences in quality scores between same-day versus different-day air contrast barium enemas for the specific parameters of quality of distention, barium coating, and amount of spasm. We conclude that when colonoscopy using air insufflation is incomplete because of looping or angulation, air contrast barium enema can be done the same day without impairing the quality of the barium study.


Status evaluation: endoscopic ultrasonography. American Society for Gastroenterology Endoscopy. Technology Assessment Committee. Endoscopic ultrasound is a new technology that improves the local staging of esophageal, gastric, and rectal carcinomas. In addition, EUS may provide useful information which will affect management in individual patients with subepithelial masses (e.g., varices, leiomyomas) and pancreatic diseases. Other imaging studies such as transcutaneous ultrasonography and CT are still necessary to detect distant metastatic disease. At present, EUS may be best reserved for use by individuals who have sufficient patient materials to provide broad experience with the technique. Physicians at centers where large numbers of patients with gastrointestinal cancer are evaluated may find this technology most useful. Even in patients with malignancy, however, studies are needed to show that the improved local staging by EUS will translate into changes in patient management and improved outcome.


Status evaluation: biliary stents. American Society for Gastrointestinal Endoscopy. Technology Assessment Committee. Large caliber plastic stents (10 to 11.5 French) have become widely accepted as an alternative to surgery in the treatment of many malignant and benign lesions of the biliary tract. Procedure-related early complications occur at an acceptable rate (8 to 10%) and procedure-related mortality is approximately 2%. Late clogging occurs at a mean of 4 to 6 months. This results in the need to change a clogged stent in 20 to 35% of surviving patients with malignant disease. In benign or malignant disease, when long-term stenting is desired, it is generally recommended to prophylactically replace the stent every 4 to 6 months to avoid clogging. While several mechanisms of clogging have been elucidated, research studies have failed to lead to a clinically available improvement in duration of patency. The role of expandable metal stents in the treatment of malignant and benign biliary strictures has not been established. Despite their large internal diameter, they may be associated with late problems related to stent clogging from tumor ingrowth or overgrowth. Technical difficulties and expense, as well as lack of data from prospective randomized trials, limit current recommendation for their use at this time.


Evaluating psychiatric consultations in the general hospital. Multivariate prediction of concordance. A study of 316 consultation cases was undertaken to examine the concordance between the psychiatric consultants' recommendations and the consultees' follow-through. Using a model of case concordance (defined as the proportion of all recommendations followed on each case), it was demonstrated that process variables, including who (the referring doctor p < or = 0.07) recommended what (psychosocial ward management p < 0.01, psychosocial diagnostic action p < 0.01, biological diagnostic action p < 0.01, aftercare p < or = 0.02, and number of recommendations p < or = 0.03), and when (timing of consultation p < or = 0.02), were the significant predictors of case concordance rather than clinical or demographic variables.


Status evaluation: sphincter of Oddi manometry. American Society for Gastrointestinal Endoscopy. Technology Assessment Committee. SO manometry appears to be helpful in defining a group of patients with biliary pain or idiopathic recurrent pancreatitis who may benefit from endoscopic or surgical treatment. It is a procedure that requires considerable time and endoscopic expertise along with knowledge of the manometric interpretation of sphincter of Oddi dysfunction. The diagnostic accuracy of SO manometry and criteria for basing therapeutic decisions on manometric findings need further study and verification.


Psychiatric affiliations between community hospitals and university programs. Transcending the difficulties. The community-based general hospital is increasingly utilized as a clinical training site for psychiatric education. Are such affiliations taken for granted by university departments? Only by careful review of the governance structure and motivations for such affiliations can a successful program be developed. Such affiliations need not be "taken for granted." Ongoing flexibility and communication will foster mutual respect between the clinical faculty within the community hospital and the university department. A case example is provided to demonstrate such a process.


Education of general practitioners in psychosomatic medicine. Effects of a training program on the daily work at Swedish primary health care centers. Two interrelated studies are reported. One reports the results of a questionnaire interview with a reference group of 51 general practitioners. The respondents express a considerable dissatisfaction with their previous medical training as it concerns their knowledge of the psychosomatic medical paradigm. The other study evaluates the effects of a 5-year education program concerning psychodynamic theories and an integrative psychosomatic approach to treatment. Six general practitioners participated in this educational program, which included both theoretical seminars and practical training in psychotherapy (under supervision) with patients suffering from chronic idiopathic pain syndrome. All the participants reported developing substantial skill in treating such patients and in handling other kinds of patients with multifactorial etiology of symptoms. The participants of the training program did not initially differ from the larger reference group as to the previous knowledge and practice in integrative psychosomatic medicine, and it may be concluded that many physicians would profit from such post-graduate training. The self-reports of all these experienced physicians also indicate that there is too little theory and practice of the psychesoma interaction in the basic medical education.


Survival of 247 liver transplant candidates. Relationship to pretransplant psychiatric variables and presence of delirium. We retrospectively gathered survival data for a cohort of previously published, prospectively studied liver transplantation candidates. Of the 247 candidates in the original cohort, 130 were transplanted at our hospital. The 117 who were not transplanted were older, had significantly more cognitive impairment on Trailmaking Tests and slowing on electroencephalogram (EEG), and had more delirium (25% vs 15%); they also had significantly more impairment in family relationships prior to transplant. Of the 130 patients who were transplanted, 91 survived as of December 1989 and 39 did not. None of the cognitive, EEG, or serum albumin results differentiated these groups, nor did age or incidence of pretransplant delirium (21% of those who died vs 12% of survivors). However, the highest level of adaptive functioning in the year prior to candidacy evaluation was significantly better in survivors; and there was more family and social dysfunction in nonsurvivors. Though the nonsurvivors received significantly more livers, histocompatibility did not distinguish the groups. The presence or absence of delirium did not predict survival status or duration for the whole group of transplanted patients. However, for the subgroup of transplant survivors, delirious patients had significantly shorter waits for transplantation and longer survival times than nondelirious ones.


Status evaluation: hot biopsy forceps. American Society for Gastrointestinal Endoscopy. Technology Assessment Committee. Monopolar hot biopsy forceps were developed for simultaneous tissue biopsy and electrocoagulation. Many endoscopists used these forceps for coagulation of diminutive polyps of the colon. The rationale for diminutive polyp eradication is to destroy neoplastic tissue and possibly prevent colon cancer. However, convincing data to document a reduction in the incidence of colorectal cancer or even complete obliteration of all treated diminutive polyps with hot biopsy forceps are lacking. Complications of hot biopsy include hemorrhage, perforation, and post-coagulation syndrome. Tissue injury is deeper with monopolar hot biopsy forceps than bipolar forceps. The right colon is particularly susceptible to transmural injury and perforation. For small polyp obliteration, comparative studies of hot biopsy (monopolar and bipolar) with other techniques such as cold biopsy combined with thermal probes, large cup cold biopsy removal, and snare electrocoagulation are warranted. The necessity to biopsy typical appearing angiomata does not seem warranted on a routine clinical basis. The expected obliteration rates of small angiomata or rates of controlling lower gastrointestinal bleeding from colon angiomata after monopolar hot biopsy electrocoagulation have not been well documented. Heater probe or bipolar electrocoagulation have been safely and effectively applied to bleeding colon angiomata. These newer coagulation probes are recommended as an alternative to hot biopsy forceps for treatment of bleeding colonic angiomata.


Psychosocial issues in hemophilia before and after the HIV crisis: a review of current research. The human immunodeficiency virus (HIV) has had a fundamental impact on quality of life, delivery of care, and directions of research efforts for the hemophilia community. Studies of psychosocial issues in hemophilia before and after the HIV crisis are reviewed. Before this crisis, research addressed personality factors and coping, family functioning, impact of psychological factors on bleeding, effects of home treatment, and school functioning. After HIV problems surfaced, research focused on psychosocial impact of the epidemic, HIV knowledge assessments, and HIV transmission prevention efforts. HIV-positive children with hemophilia have not received sufficient attention. Future directions for research are suggested.


A retrospective study of self-inflicted burns. A study was conducted of all 51 patients admitted on 64 occasions with self-inflicted burns to the Welsh Regional Burns Unit between January 1979 and January 1991. Two different groups of patients were identified, namely, patients who attempted suicide and patients with self-mutilative behavior. Their differences on a number of variables are described. At follow-up, no patient had subsequently committed suicide, but the majority of suicide attempters remained in contact with psychiatric services. In view of the considerable psychiatric morbidity of this patient group there is a need for consultation-liasion psychiatrists to provide a service to Burn Units.


Autogenic training and self-hypnosis in the control of tension headache. This study compares autogenic training and training in multiple self-hypnosis strategies in a sample of 56 patients diagnosed as having chronic tension headache on the basis of medical evaluation by a neurologist. At posttreatment and follow-up, no differences between the two treatment regimens in the reduction of headache and psychological distress were observed. During treatment, patients reduced their headache activity and level of psychological distress significantly in contrast to the waiting-list period (p < 0.05). Follow-up measurements indicated that therapeutic improvement was maintained (p < 0.05). Short-term and long-term pain reduction was accompanied by an increase in perceived pain control (p < 0.003). Moreover, those patients who attributed the pain reduction obtained during therapy to their own efforts manifested long-term pain reduction (p < 0.003).


Metoclopramide-associated tardive dyskinesia in hemodialysis patients with diabetes mellitus. Two case reports. Metoclopramide, a drug used almost exclusively for medical indications, is a dopamine (D-2) receptor blocker and has been reported to cause extrapyramidal side effects. We present two case reports of hemodialysis patients who were treated with metoclopramide for diabetic gastroparesis. Within 12 months of beginning treatment, both patients developed persistent tardive dyskinesia. These cases highlight the fact that some patients who benefit from metoclopramide may also have a relatively high risk of developing persistent tardive dyskinesia. The consultation-liaison psychiatrist can play an important role in the education of the medical staff regarding metoclopramide-induced tardive dyskinesia.


The association of panic/agoraphobia and asthma. Contributing factors and clinical implications. The point prevalence of phobic anxiety disorders was determined in 107 asthmatic outpatients through a standardized psychiatric interview and DSM-III-R diagnostic criteria. Agoraphobia and panic disorder were more prevalent (13.1% and 6.5%, respectively) than in the general population. Contributing factors and the clinical implications of this association are discussed. The recognition of specific anxiety syndromes enhances the efficacy of the treatment of anxious asthmatic patients.


[A method for determining the presence of inverted repeats in the chloroplast genome of higher plants]. A plasmid containing fragments of rp12 and rps19 genes from the chloroplast genome of Arabidopsis thaliana was developed. The presence of inverted repeats in the chloroplast DNA of A. thaliana and Vicia sativa, and their absence from two species of Fabaceae family (Lathyrus sativus, Lens esculenta) were shown with the help of this plasmid.


[Disorders of finger flexion crease formation in various congenital anomalies of human development]. Deviations in finger flexion crease formation and ridge counts were analysed in normal and deformed (Down syndrome, arthrogriposis, diastrophic dysplasia) hands. Certain interrelation was found between decrease in the ridge count and the number of the finger flexion creases in Down syndrome. The changes observed agree with the hypothesis that intersegmental borders, and later, the joints and finger flexion creases are laid out on the basis of the positional information which is directed by morphogenetic gradients. This model enables us to interpret more or less unequivocally the changes in flexion creases in patients with arthrogriposis and diastrophic dysplasia (dwarfism).


[Ploidy level in Streptomyces cerevisiae strain 15B-P4 strain]. Hybridization analysis of seven clones of Saccaromyces cerevisiae 15B-P4 strain, which were obtained from different cultures, was carried out. Yeast strains taken from the Peterhoff breeding stocks were kept in the laboratory of genetics at Biological Institute of Irkutsk University from 1970. Increase in the number of prototrophic segregants was shown to by the result of aneuploidy (2n + 1) in the hybrids under study. Aneuploidy was revealed for the chromosomes I, III, IX, XII. Disomic clones of 15B-P4 strain were unstable.