Comparison of a swim-up technique with the Hamilton Thorn Motility Analyser for measurement of sperm velocity and motility. A colorimeter-based swim-up (SU) technique was developed and compared with a Hamilton Thorn Motility Analyser (HTM) for the evaluation of ram semen. SU parameters (sperm velocity in microns s-1, proportion of rapidly moving spermatozoa, and motility index) were significantly correlated (r from 0.47 to 0.98, P from < 0.05 to < 0.001) with most HTM parameters in semen containing known proportions of motile and immotile spermatozoa and in semen that was cold shocked, aged, diluted-stored and frozen-thawed. There were, however, no significant correlations between sperm velocity and HTM parameters in the fresh semen studied, possibly because of the small number of observations (n = 21) and narrow range of semen quality (83 +/- 2% subjectively scored motility) available. It is concluded that the swim-up technique is a simple, cheap, objective and reliable means of measuring sperm velocity and motility in ram semen.


Effects of the progesterone antagonist RU486 on myometrial activity in vivo in early pregnant and pseudopregnant rats. Myometrial activity in vivo was quantified by video-laparoscopy in early pregnant rats given doses of RU486 which caused embryo abortion and blocked the action of progesterone on the vagina. All treatments diminished the frequency of circular contractions and abolished the curling movements of the uterus which are characteristic of pregnant, pseudopregnant and progestin-treated rats. The effects of RU486 on circular contractions were similar in pseudopregnant rats, i.e. they were not a consequence of embryo abortion. These results support the thesis that increased myometrial circular contractions in early pregnancy and pseudopregnancy are induced by increasing levels of progesterone. Effects of RU486 on longitudinal contractions were more complex: the highest dose inhibited longitudinal contractions on Day 5 of pregnancy and pseudopregnancy, but increased their frequency on Day 6. The acute inhibition of longitudinal contractions by RU486 was unexpected and the mechanism remains to be elucidated. The later increase in the frequency of longitudinal contractions appears to be due to antagonism of progesterone by RU486. The frequency of caudal longitudinal contractions on Day 6 in mated rats given RU486 was similar to that in unmated oestrous rats, but the frequency of cranial longitudinal contractions was significantly higher. These results support the hypothesis that stimuli received during copulation may have long-term effects on myometrial activity, by increasing pacemaker activity at the cervix.


Addition of superoxide dismutase and catalase does not necessarily overcome developmental retardation of one-cell mouse embryos during in-vitro culture. There is evidence that developmental blocks observed in mouse embryos during culture in vitro may be the result of free radical-induced cellular dysfunction. We have further investigated this possibility by examining the effects of 5% O2 and the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), on mouse 1-cell embryo development. The results demonstrate that development of CF-1 strain embryos is enhanced by incubating in 5% CO2, 5% O2, 90% N2 (5/5/90) compared with 5% CO2 in air (5/air) (P < 0.01) and by culturing in the presence of other embryos. Superoxide dismutase significantly improved embryonic development (35 +/- 5% v. 17 +/- 4% morulae/blastocysts, P < 0.001) at a concentration of 100 units mL-1 when embryos were gassed under 5/5/90. At a concentration of 1000 units mL-1, SOD was detrimental to development (P < 0.001). Injection of SOD and/or CAT into embryos had not effect on development. Development has also been examined in four strains of mice (CF-1, Quackenbush (random-bred strains), Balb-C (inbred) and the F1 hybrid of CBA x C57B1) in the presence or absence of 100 units SOD mL-1 and 1000 units CAT mL-1. Embryonic development was markedly different among the four strains examined, with F1 hybrid > Balb-C (P < 0.001), Balb-C > CF-1 (P < 0.05) and Quackenbush embryos performing very poorly compared with the embryos of the other three strains (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of the SpermMar test with currently accepted procedures for detecting human sperm antibodies. To eliminate the possibility of immunological infertility in spontaneously infertile and re-anastomosed men, a screening test that can be applied directly to semen is desirable. The SpermMar test is one such possibility. In this study, indirect tests for sperm antibodies using the commercial SpermMar test have been applied to a panel of sera whose reactions in the tube slide agglutination test (TSAT), gelatin agglutination test (GAT) and sperm immobilization test (SIT) for sperm antibodies are well characterized. The results from the SpermMar tests are compared directly with those obtained from Immunobead tests carried out at the same time. Results from screening tests performed on 30 sera confirmed complete correspondence between the GAT, SpermMar and Immunobead tests. When sera were titrated, the Immunobead test proved slightly more sensitive than the GAT and the SpermMar test was slightly more sensitive than the Immunobead test. The SpermMar test proved easier to use and to assess than the Immunobead test and it is recommended for consideration as a screening procedure for sperm antibodies despite the fact that at this stage only IgG antibodies can be detected.


Characterization and autoradiographic localization of the epidermal growth factor receptor in the jejunum of neonatal and weaned pigs. Receptors for epidermal growth factor (EGF) were characterized on the intestinal membranes of newborn, sucking and weaned pigs. 125I-labelled EGF (125I-EGF) binding to membrane homogenates was time-dependent, saturable, linearly correlated to membrane protein and reversible. Analysis of saturation curve data revealed a single class of 125I-EGF binding sites in both newborn and weaned pigs. Receptor levels tended to be higher in weaned than in newborn pigs; the converse was true for the receptor affinity. In contrast, virtually no binding sites were found on the intestinal membranes of sucking pigs. Autoradiography in vitro of jejunal sections of newborn and weaned pigs demonstrated 125I-EGF receptors on both microvillar and basolateral surfaces of enterocytes, suggesting that luminal EGF could influence developmental processes in the intestine either directly or indirectly following transcytosis of the ligand.


Differential mRNA expression of the phosphoprotein p19/SCG10 gene family in mouse preimplantation embryos, uterus, and placenta. The p19/SCG10 gene family encodes two structurally related cellular proteins that are implicated in signal transduction during differentiation of mammalian cells. Previous evidence suggests that both genes are expressed in a stage-specific manner but that expression of p19 is widespread, whereas that of SCG10 is restricted to developing neurons. To determine at which developmental stage these two genes are first expressed, we have probed for mRNA transcripts in preimplantation embryos and the utero-placental unit of the mouse. As determined by polymerase chain reaction (PCR) to amplify reverse-transcribed RNA, expression of both genes was detected in preimplantation embryos, although the temporal pattern was distinct. p19 mRNA appeared transiently in 2-cell embryos, was undetectable in morulae and early blastocysts and reappeared in expanded blastocysts. In contrast, embryonic expression of SCG10 mRNA commenced in morulae and was maintained through to the blastocyst stage. Interestingly, only SCG10 expression could be detected in blastocysts derived from cultures of 2-cell embryos. During the post-implantation period, SCG10 transcripts were only detected in the uterus and placenta by reverse transcriptase-PCR, whereas p19 mRNA could be detected by Northern blotting and showed stage-specific expression in both tissues. The data confirm that, at later developmental stages, expression of p19 is widespread while that of SCG10 is more restricted. The expression of both genes in preimplantation embryos suggests distinct but possibly overlapping roles for p19 and SCG10 in early mammalian development.


Duration of the cycle of the seminiferous epithelium and quantitative histology of the testis of the South American white-belly opossum (Didelphis albiventris), Marsupialia. The duration of the cycle of the seminiferous epithelium of the South American white-belly opossum, as obtained by autoradiography after intratesticular injection of tritiated thymidine, was estimated to be 17.3 +/- 0.1 days (mean +/- s.d.). Quantitative histological analysis was performed on testes from animals caught both in mating and non-mating periods of the annual reproductive cycle. Significant differences were found in the volumetric proportion of Leydig cells, but the spermatogenic yield remained constant throughout the year. The numerical ratio between type A spermatogonia and zygotene primary spermatocytes (1:12.0), as well as daily sperm production (4.8 x 10(6) sperm cells per g of testis parenchyma per day), were found to be lower than those reported in most eutherian mammals.


Monoclonal anti-idiotypic antibody to progesterone with internal image properties. An auto-anti-idiotypic approach was used to generate mouse monoclonal anti-idiotypic antibody E9F11F6 (Ab2) to progesterone. A conjugate of 4-pregnane 3,20 dione and bovine serum albumin was used as the immunogen. E9F11F6 bound to a rabbit anti-progesterone antibody in a linear concentration-dependent manner. It inhibited the binding of [3H]progesterone to a monoclonal anti-progesterone antibody, E9D5 (Ab1); this inhibition was concentration dependent. Results from chase experiments showed that this inhibitory activity of Ab2 was not due to steric hindrance but was a result of direct binding to the ligand combining site. Indirect immunofluorescence studies also showed that Ab2 and progesterone bound to similar binding sites on Ab1. Overall, the results suggest that E9F11F6 contains an internal image of at least part of the progesterone molecule, and that it can be classified as an Ab2 beta antibody. This anti-idiotypic antibody may be of value in further studies of endocrine and reproductive physiology.


Differential pituitary response to GnRH in pregnant Booroola-Assaf and Assaf ewes. Pituitary response to exogenous gonadotrophin-releasing hormone (GnRH) was examined at a late stage of pregnancy in 10 Booroola-Assaf ewes heterozygous at the FecB locus (FecBFec+) and in 11 Assaf ewes that were non-carriers (Fec+Fec+). Basal plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations were similar in the two genotypes. Administration of 100 micrograms of GnRH resulted in a significant increase (P < 0.05) in plasma LH and FSH concentrations in most of the ewes treated. Maximal responses were observed 105-135 min after GnRH treatment. Pituitary responses to GnRH were significantly lower (P < 0.05) in Booroola-Assaf than in Assaf ewes. The decreased pituitary responsiveness observed in FecB gene carriers compared with Fec+Fec+ ewes might be due to differences in the concentrations of ovarian or uterine hormones modulating the release of gonadotrophin. The results suggest that FecB-specific differences can be observed at the pituitary level.


Effect of ovariectomy on blastocyst expansion and survival in ferrets (Mustela putorius furo). The initial objective was to investigate whether progesterone alone can support full blastocyst expansion in ferrets ovariectomized on Day 5 post coitum (p.c.). By Day 11 p.c. blastocysts from control animals had expanded to approximately 2000 microns in diameter, whereas by Days 11 or 14 p.c. blastocysts from ovariectomized animals given progesterone had diameters of < 1000 microns. Thus, ovarian factors in addition to progesterone are apparently required for normal blastocyst expansion in this species. Subsequent experiments indicated that an initial stage of expansion (from approximately 200 microns to approximately 400 microns) occurred regardless of whether ovariectomy was performed on Day 2 or 3 p.c. A second stage of expansion resulted in blastocysts of approximately 700 microns in diameter and it occurred in ovariectomized animals if progesterone was given or if ovariectomy was delayed until Day 5 p.c. A third phase of expansion resulted in blastocysts of approximately 2000 microns in diameter and occurred only if ovariectomy was delayed until Day 8 p.c. Although blastocyst expansion appeared normal in these animals, implantation did not occur in the absence of progesterone replacement. In addition, blastocysts retained in the oviduct by ligation of the uterotubal junction failed to expand beyond approximately 400 microns in diameter. These results suggest that progesterone acts upon the uterus to promote blastocyst expansion up to a diameter of approximately 1000 microns and that additional ovarian factors are required for further blastocyst expansion.


Oviductal fluid protein patterns in the rhesus monkey (Macaca mulatta) during the menstrual cycle. Oviducts were obtained from monkeys on Days 8, 14, 19 and 25 of the menstrual cycle and changes in the pattern of luminal fluid proteins were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Densitometric analysis after periodic acid Schiff's reagent (PAS) and coomassie blue staining of the gels revealed 85 and 95 kDa proteins only up to Day 14 whereas a 130 kDa glycoprotein persisted up to Day 19 and reached a nadir at mid-menstrual cycle (Day 14). The absence of the 130 kDa glycoprotein in the serum and its presence in cytosolic preparations up to Day 19 suggest that it is of oviductal origin. The 130 kDa glycoprotein is of particular interest since it was present in the oviductal fluid during mid cycle, a period when the oviduct participates in gamete transport, fertilization and embryo development. The conclusion drawn from this study is that the protein profile of monkey oviductal fluid changes during the menstrual cycle.


Early endometrial microvascular response during implantation in the rat. The endometrial microvasculature becomes intimately involved in the events of early implantation. This paper reviews aspects of this microvascular involvement during implantation in the rat. There is a major increase in vascular permeability surrounding the implanting embryo, leading to significant local changes in microvascular architecture. This is followed by a shutdown of the capillaries closest to the embryo as the primary decidual zone develops. At this time, endometrial capillaries adjacent to the primary decidual zone become dilated, with over twice the average diameter of intersite capillaries. Endometrial neutrophils are reduced around the implanting blastocyst, mitigating against a role for these inflammatory mediators in vascular aspects of the implantation process. Angiogenesis does not appear to increase at the implantation site, although there is an increase in production of endometrial endothelial cell migratory signal a few hours prior to the commencement of implantation.


Morphometric and freeze fracture studies of human endometrium during the peri-implantation period. This paper reviews recent morphological work on peri-implantation endometrium collected from the Monash University In vitro Fertilization (IVF) Programme. Comparisons of endometrial tissue collected from women who had undergone different superovulation regimens demonstrated that significant structural differences could be detected by morphometry and ultrasound, but not by routine histopathology. Morphometric studies on endometrium from agonadal women receiving hormone replacement therapy demonstrated major differences between women with identical endocrine profiles. A biopsy inadvertently taken from one of these patients at the time of implantation was not of the appearance classically believed to be associated with receptivity for implantation. Studies have shown that the tight junction structure of endometrial epithelium is regulated during the menstrual cycle, suggesting that the integrity of the epithelial barrier may be important in the preparation of the endometrium for implantation.


Glycoconjugates as positive and negative modulators of embryo implantation. A variety of studies indicate that complex glycoproteins participate in or modulate adhesive interactions occurring during embryo implantation. In particular, proteoglycans and proteins that bind proteoglycans are involved at multiple stages of this process. Identification of these binding proteins and the molecular controls over glycoconjugate expression are required to develop a comprehensive understanding of the implantation process.


Studies in vitro of effects of steroid hormones and the blastocyst on endometrial function in the sheep. Normal endometrial function is a result of regulation by the combination of ovarian steroids and local agents arising from within the embryo-maternal unit. We have used in vitro techniques to examine the role of steroid hormones and ovine trophoblast interferon on endometrial function in the ewe. Immunolocalization of oestrogen receptors in endometrial tissue demonstrated marked changes throughout the cycle and in early pregnancy with maximal concentrations during the follicular and very early luteal phases. Protein secretion from highly purified cultured ovine stromal and epithelial endometrial cells, and the direction of secretion from polarized epithelial cells, has been examined by incorporation of [35S]methionine and by one- and two-dimensional gel electrophoresis. Protein synthesis is greater in stromal than in epithelial cells and more protein is secreted apically than basally from epithelial cells. A number of common and some different proteins are secreted by the two cell types. One secreted protein is matrix metalloproteinase-3 (stromelysin) which degrades components of basement membranes. Ovine trophoblast interferon attenuates the production of prostaglandins from ovine endometrial cells but its action is not by an effect on localization or concentration of the enzyme prostaglandin synthase or on expression of the gene for prostaglandin synthase. Such studies in vitro contribute to our understanding of how the endometrium is prepared for implantation.


Embryo-derived platelet activating factor. Platelet-activating factor (PAF) is secreted by the preimplantation embryo of a number of species. The role of this secretion is yet to be fully elucidated. Evidence to date indicates that it has an important function as an autocrine stimulant of embryonic metabolism, growth and viability. Production of PAF by embryos appears to be severely compromised in vitro. This may be a major cause of reduced embryo viability following embryo culture and it may also help to explain the controversy in the literature regarding the production of PAF by embryos. PAF also alters several aspects of maternal physiology during early pregnancy including endometrial prostaglandin secretion. The significance of these changes remains to be defined.


Roles of prostaglandins (PG) F2 alpha, E1, E2, adenosine, oestradiol-17 beta, histone-H2A and progesterone of conceptus, uterine or ovarian origin during early and mid pregnancy in the ewe. Pregnancy does not prevent the local transfer or accumulation of prostaglandin F2 alpha (PGF2 alpha) by the corpus luteum (CL), the number of receptors for PGF2 alpha or the binding of PGF2 alpha to the CL. However, the conceptus does depress the response of the CL to PGF2 alpha during early pregnancy. PGE1 and PGE2 appear to be blood-borne antiluteolysins that are delivered locally to prevent the actions of PGF2 alpha during early pregnancy, since they prevent luteolysis only when given by chronic intrauterine infusion adjacent to the ovary with the CL. The concentrations of PGE1 and PGE2 in the endometrium and PGE2 in uterine venous plasma increase during early pregnancy. A Day 10 embryo transferred to a Day 6 progestagen-primed recipient ewe advances the time at which PGE2 is secreted. The uterine venous PGE/PGF2 alpha ratio is 12:1 at midgestation, and exogenous PGF2 alpha increases the placental secretion of oestradiol-17 beta. This is followed by increases in PGE secretion when endogenous PGF2 alpha increases. Both oestradiol-17 beta and PGE may protect placental secretion of progesterone from PGF2 alpha, since PGF2 alpha causes the CL to regress but does not affect placental progesterone or pregnancy in the presence or absence of the ovary.


Nutrition-progesterone interactions during early pregnancy in sheep. A series of studies was undertaken to determine the relationship between level of feed intake during early pregnancy, concentrations of peripheral progesterone and embryo survival in sheep. Ewes fed twice maintenance (2M) rations after joining had a pregnancy rate of 48%. Ewes fed 2M rations and given exogenous progesterone between 8 and 14 days after mating had a pregnancy rate of 76%. Ewes fed rations calculated to maintain live weight (maintenance, M) or fed restricted rations during this same time had pregnancy rates ranging from 60 to 68%, with no beneficial effect of progesterone supplement. Concentrations of peripheral plasma progesterone on Day 12 after mating were inversely related to the level of feed intake; this relationship reflected an increase in the metabolic clearance rate of progesterone with increased feed intake (1/2M, M and 2M) without concomitant changes in the entry rate of the hormone. Injection of epostane, an inhibitor of the enzyme 3 beta-hydroxysteroid dehydrogenase, caused 'windows' of progesterone reduction for 48-h periods over Days 9-13 after mating. The sheep embryo was sensitive to low peripheral plasma progesterone concentrations only on Days 11 and 12 after mating. Blood flow rates in the portal vein of ewes fed either 1/2M, M or 2M rations for 7 days were directly related to the level of feed intake.(ABSTRACT TRUNCATED AT 250 WORDS)


Endocrine events associated with endometrial function and conceptus development in cattle. Regulation and timing of luteolysis during the bovine oestrous cycle is controlled by the initiation and length of progesterone stimulation. Results have demonstrated that early administration of progesterone shortens the interoestrous interval in the ewe and cow, and removal of progesterone stimulation through a progesterone receptor antagonist delays luteolysis in sheep. Current data suggest that down-regulation of progesterone receptors in the uterine epithelium may initiate events involved in the synthesis and release of prostaglandin F2 alpha (PGF2 alpha) for luteolysis. Progesterone is also involved in the stimulation of the uterine secretions that regulate conceptus growth and the release of the bovine trophoblast protein-1 (bTP-1) necessary for inhibiting endometrial PGF2 alpha release. Conceptus secretion of bTP-1, a Type I trophoblast interferon, increases the concentration of the cellular enzyme 2',5'-oligoadenylate synthetase within the endometrium. The biological role of 2',5'-oligoadenylate synthetase in the establishment of pregnancy is discussed.


Uterine secretion of prostaglandin F2 alpha in the ewe: regulation at the cellular level by ovarian hormones and the conceptus. Changes in the ability of the uterus to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin may play a critical role in determining when endogenous secretion of PGF2 alpha begins. The cellular mechanisms that regulate uterine secretion of PGF2 alpha in response to oxytocin have not been completely defined. Several intracellular components that may contribute to this regulation have been studied, including phospholipase C (PLC), prostaglandin H endoperoxide synthase (PGS) and receptors for oxytocin. All of these components change during the oestrous cycle and are associated with the development of uterine secretory responsiveness to oxytocin. Progesterone appears to play the principal role in regulating oxytocin receptors, PLC and PGS. The conceptus appears to suppress the increase in receptors for oxytocin and PLC activity that typically occurs around the time of luteal regression.


Genes for the trophoblast interferons and their distribution among mammals. The trophoblast interferons (IFN), ovine and bovine trophoblast protein-1 (oTP-1 and bTP-1 respectively), possess many properties in common with other Type I IFN, including antiviral and antiproliferative activities. However, they differ from other IFN subtypes in terms of their specific pattern of expression and poor responsiveness to viral stimulation. We describe here data that suggest that the trophoblast IFN genes are also distinct from other Type I IFN genes with respect to species distribution, promoter organization and transcriptional regulation. These results have important implications in terms of trophoblast IFN gene evolution and add credence to the concept that the trophoblast IFN genes are a distinct IFN gene subtype well suited for their role in early pregnancy.


Neutral endopeptidase modulates endothelin-1-induced airway smooth muscle contraction in guinea-pig trachea. This study was designed to evaluate the role of neutral endopeptidase (NEP) in modulating the airway smooth muscle contraction induced by endothelin-1 in isolated segments of guinea-pig trachea. Endothelin-1 (10(-9)-10(-6) M) produced a concentration-dependent contraction that reached a maximum by 30 min. The NEP inhibitor leucine-thiorphan (10(-5) M) significantly increased the contractile response to endothelin-1. The addition of leucine-thiorphan to tracheal segments precontracted by 10(-9) and 10(-8) M endothelin-1 increased isometric tension by 181 +/- 65% (mean +/- 1 S.E.M.; P less than 0.05) and by 138 +/- 49% (P less than 0.05), respectively. In contrast, the kininase II inhibitor captopril and the peptidase inhibitors leupeptin and bestatin had no effect. Preincubation of endothelin-1 with 1 microgram recombinant human NEP decreased the contractile activity of endothelin-1 by 72 +/- 9%, whereas no effect was observed using heat-inactivated NEP. We conclude that NEP modulates endothelin-induced contraction of airway smooth muscle in the guinea-pig trachea.


Different relative abundance of neurotensin and neuromedin N in bovine ocular tissues. Neurotensin (NT) and neuromedin N (NN) are regulatory peptides encoded by the same gene and located in tandem within a common precursor. Using specific radioimmunoassays for both peptides, their relative abundance in extracts of bovine ocular tissues has been examined. Within the retina, the molar concentration of NN was significantly higher (P less than 0.001) than that of NT. In contrast, within both choroid/sclera and iris/ciliary bodies, the molar concentration of NT was significantly higher (P less than 0.001) than that of NN. These data demonstrate that the theoretical molar ratio of 1:1, which would result from complete processing of both peptides from the common precursor, does not occur in any of the ocular tissues examined. Reverse phase HPLC of extracts of each ocular tissue confirmed the differential abundance of NT and NN. These data would suggest that the common NT/NN precursor is differentially-processed within bovine ocular tissues, a finding which may be of physiological significance.


The effect of TGF alpha on intestinal solute transport. The effect of transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) on 3-O-methylglucose transport was examined in vitro under short-circuited conditions in stripped rabbit jejunum. Mucosal EGF, 60 ng/ml, stimulated a significant increase in net 3-O-methylglucose transport (Jnet 0.67 +/- 0.15 vs. 0.90 +/- 0.15 microEq/cm2/h; P less than 0.03; n = 6) due to an increased mucosal to serosal flux (Jms 1.2 +/- 0.2 vs. 1.5 +/- 0.2 microEq/cm2/h; P less than 0.03). In contrast, TGF alpha, when applied to both mucosal and serosal surfaces at concentrations of either 60 (n = 6) or 150 (n = 9) ng/ml had no effect on either mucosal to serosal (Jms) or net transport (Jnet) of 3-O-methylglucose. TGF alpha did induce a significant increase in the serosal to mucosal flux (Jsm 60 ng/ml 0.44 +/- 0.02 vs. 0.51 +/- 0.03, 150 ng/ml 0.55 +/- 0.03 vs. 0.64 +/- 0.05 microEq/cm2/h; P less than 0.05). When brush border surface area was examined after exposure to either 60 ng/ml TGF alpha or saline vehicle for 2 h in in vivo isolated jejunal loops no significant difference was found (control 53 +/- 1.9; n = 35 vs. TGF alpha 52 +/- 1.9 microns 2; n = 29). Bioactivity of transforming growth factor alpha was assessed by an gastric acid secretion bioassay and found to be intact. These data provide further evidence for separate and distinct functional roles for these peptides in some biological systems.


Influence of VIP on the number of enterochromaffin and mucosal mast cells in the colon of the rat. The possibility that VIP (Vasoactive intestinal peptide) could influence the enterochromaffin (EC) cell secretion of serotonin (5HT) and the action of VIP on the mast cell population of lamina propria were investigated in Wistar rat colon infused with a short chain fatty acid solution (sodium acetate), during a 1 h period. Under the action of an intravenous injection of synthetic porcine VIP, 14 micrograms/kg/h), the number of EC cells diminished significantly in the cecum and left colon, when compared to non-injected animals, both infused with a sodium acetate solution. At the same time, the number of mucosal mast cells in the crypts and lamina propria decreased significantly in the cecum. The postulate we put forward is that these VIP-induced changes are exerted through the stimulation of 5HT released from EC cells not only under normal physiological conditions but probably also under pathological conditions.


Immunodetection of secretogranin II in animal and human tissues by new monoclonal antibodies. Secretogranin II (chromogranin C) is an acidic tyrosine-sulfated secretory protein, known to be a marker of neuroendocrine secretory products and of specific neuroendocrine tumours. In order to obtain anti-secretogranin II monoclonal antibodies for cell biology studies and, in particular, for clinical applications, we immunized mice with a secretogranin II-enriched fraction prepared from homogenates of bovine anterior pituitaries. Hybridoma supernatants obtained from the splenocytes of a hyperimmune mouse, screened with an enzyme-linked immunosorbent assay, were analyzed by both immunocytochemistry and two-dimensional immunoblotting. By using this experimental approach, we were able to identify two monoclonal antibodies (8G1 and 5A7) which recognize bovine secretogranin II. Both immunocytochemistry and immunoblotting revealed that one of them, the 5A7 antibody, cross-reacts with the human antigen. The distribution patterns of the immunoreactivity, obtained by immunocytochemistry with the 5A7 antibody in animal and human tissues, partially overlap those, obtained by using a polyclonal antiserum elicited against bovine secretogranin II, previously described. Moreover, the 5A7, but not the polyclonal antibody, reacts with some duodeno-jejunal cells. In conclusion, both the 5A7 and 8G1 antibodies can be useful for cell biology studies. The 5A7 antibody can be used for the detection of secretogranin II in human tissues and should be of help in clinical and pathological practices.


Neuropeptide Y 16-36 inhibits mucociliary activity but does not affect blood flow in the rabbit maxillary sinus in vivo. Recent investigations have shown neuropeptide Y (NPY) to be present in the rabbit maxillary sinus, and NPY is known to be released upon sympathetic nerve stimulation. To study, in vivo, the effect on mucociliary activity and blood flow, NPY 1-36 and some of its analogues were injected intra-arterially. The effects of the Y1/Y2 agonist NPY 1-36 was compared with the ones of the Y2 agonist NPY 16-36, the Y1-agonist [Leu31,Pro34]NPY and the Y1/Y2 agonist peptide YY. Mucociliary response was recorded photoelectrically and expressed as a percentage of the basal mucociliary activity immediately prior to challenge. The effect on blood flow was measured with laser Doppler flowmetry and expressed as a percentage of the mean blood flow during the 60 s preceding challenge. NPY 1-36 and NPY 16-36 both reduced mucociliary activity dose-dependently at equimolar dosages (0.024-1.2 nmol/kg). The greatest effect was seen after the highest dosage tested. NPY 1-36 reduced mucociliary activity by 14.6 +/- 1.8%, and NPY 16-36 by 13.2 +/- 1.4%. At the highest dosage tested the Y1 receptor agonist [Leu31,Pro34]NPY did not significantly reduce mucociliary activity, whereas PYY reduced mucociliary activity by 15.0 +/- 1.8%. Injections of NPY 16-36 had no effect on blood flow whereas NPY 1-36, [Leu31,Pro34]NPY and PYY all reduced blood flow dose-dependently. Maximal decrease was seen at the highest dosage tested and was 47.1 +/- 5.4%, 70.4 +/- 7.4% and 58.2 +/- 8.4%, respectively. These findings suggest the mucociliary effects to be mediated via Y2 receptors whereas blood flow is regulated via Y1 receptors.


Effect of chymotrypsin on human cholecystokinin release: use of clostripain in the validation of a new radioimmunoassay. We have developed and validated a new radioimmunoassay for cholecystokinin. In order to establish that the antiserum binds large and small forms of CCK to an equal extent, we used the microbial enzyme clostripain, which cleaves large forms of CCK yielding CCK 8. Cleavage by clostripain of synthetic and purified forms of CCK, and CCK extracted at from human jejunum and CCK in human plasma was found not to affect immunoactivity, indicating that the antiserum reacts similarly with all forms of CCK. There is controversy over whether intraduodenal trypsin inhibits release of CCK in man. We used our radioimmunoassay to investigate whether chymotrypsin, rather than trypsin, could be the major mediator of negative feedback control of CCK release. Six normal subjects received an intraduodenal infusion of L-phenylalanine and L-tryptophan on two occasions, with the addition of either 1 g/l bovine chymotrypsin or 1 g/l albumin. Plasma CCK concentrations rose in response to the amino acid infusion, but were not affected by the addition of chymotrypsin, indicating that this enzyme is not a mediator of CCK feedback regulation in man.


Cardiovascular and respiratory actions of pituitary adenylate cyclase-activating polypeptides. Effects of pituitary adenylate cyclase-activating polypeptide (PACAP38) and PACAP27 on the cardiovascular and respiratory systems were examined and compared to those of vasoactive intestinal polypeptide (VIP) in anesthetized beagle dogs. Intravenous PACAP27 and PACAP38 produced a decrease in mean arterial blood pressure (MBP), and an increase in both femoral arterial blood flow (ABF) and in frequency of respiration (FR) with a dose-dependent relationship between 10 and 300 pmol/kg. PACAP27 produced a dose-dependent increase in heart rate (HR) between 10 and 300 pmol/kg while PACAP38 induced tachycardia which was not dose-dependent. Administration of 300 pmol/kg PACAP38 and PACAP27 produced extreme hypertension after transient hypotension. PACAP38 produced severe bradycardia after transient tachycardia. The cardiovascular actions of PACAP38 were persistent compared to those of PACAP27. Intravenous injection of 10-300 pmol/kg VIP brought about hypotension, tachycardia and an increase in ABF and FR with a dose-dependent relationship. VIP, at 2000 pmol/kg, did not produce the biphasic response obtained by a large dose of PACAP38. The present studies demonstrate that PACAP partially possesses VIP-like cardiovascular and respiratory actions and that the C-terminal 11 amino acid residues of PACAP38 are presumably responsible for a prolongation of its actions.


Functional control of chromogranin A and B concentrations in the body of the rat stomach. The chromogranins are soluble, acidic, proteins which are frequently co-stored in neuroendocrine cells with biogenic amines. In the gastric mucosa chromogranin A is localized to enterochromaffin-like cells which are the main source of histamine, and which are known to be regulated by circulating gastrin. We have used radioimmunoassays selective for the extreme C-terminal regions of chromogranin A and B to examine changes in gastric extracts following modulation of the gastric luminal contents. There were decreased concentrations of the two chromogranins in tissue extracts of rats after food withdrawal (which lowered plasma gastrin concentrations); inhibition of acid secretion with the H+/K(+)-ATPase inhibitor, omeprazole (which increased plasma gastrin concentrations) raised chromogranin A and B concentrations both in fasted rats, and in rats fed ad libitum. There was no evidence for altered patterns of posttranslational cleavage of chromogranin A or B with these treatments. The data indicate that chromogranin A and B concentrations in gastric ECL cells are regulated in parallel with histamine production, and are consistent with the idea that the chromogranins play a role in the formation and stabilization of the secretory granule involved in amine storage.


Vasoactive intestinal polypeptide (VIP) inhibits rat alveolar macrophage phagocytosis and chemotaxis in vitro. Vasoactive intestinal polypeptide (VIP) has been shown to inhibit lymphocyte function and is believed to modulate the immune response. We explored the possible immunomodulatory effects of VIP on alveolar macrophage (AM) function by examining its influence on AM phagocytosis and chemotaxis. Rat AMs were collected by bronchoalveolar lavage and incubated for 90 min with polystyrene beads in the presence or absence of VIP in concentrations from 10(-11) M to 10(-5) M. VIP significantly (P less than 0.0001) inhibited AM phagocytosis of polystyrene beads at concentrations of 10(-11) to 10(-6) M, with a maximal inhibition of 35% at 10(-6) M (but no inhibition at 10(-5) M). AMs were also incubated for 90 min in a chemotaxis chamber with endotoxin-activated rat serum (EARS) as a chemoattractant, with or without VIP in concentrations from 10(-9) to 10(-6) M. VIP significantly (P less than 0.0001) inhibited AM chemotaxis by at least 30% at concentrations of 10(-9) to 10(-6) M, with a maximal inhibition of 46% at 10(-7) M. These results indicate that VIP, in concentrations from 10(-11) to 10(-6) M, inhibits rat AM function as assessed by phagocytosis of polystyrene beads and chemotaxis to EARS. The inhibition of alveolar macrophage function is another mechanism by which VIP may modulate the immune response in the lung.


Unlike VIP, the VIP-related peptides PACAP, helodermin and helospectin suppress electrically evoked contractions of rat vas deferens. We have compared the effects of vasoactive intestinal peptide (VIP) and of the VIP-related peptides pituitary adenylate cyclase activating peptide (PACAP) 1-27 and 1-38, helodermin, helospectin I and helospectin II, on the electrically evoked twitches in the isolated vas deferens of the rat. While VIP was virtually without effect, PACAP 1-38 suppressed the electrically evoked twitches effectively and in a concentration-dependent manner (pIC50 value 7.5). The naturally occurring N-terminal fragment PACAP 1-27 was less effective than PACAP 1-38 (Imax values 37.2% suppression compared to 76.5%) and less potent. The C-terminal fragment PACAP 16-38 was virtually inactive. Also helodermin and helospectin I+II suppressed the electrically evoked twitches effectively and in a concentration-dependent manner (pIC50 values 6.9; 7.2; 6.8, respectively). The three peptides produced similar maximum reduction of the twitches (74-80%). The findings suggest that PACAP, helodermin and helospectin suppress the electrically evoked contractions in the rat vas deferens via receptors distinct from VIP receptors.


Difference between the antisecretory mechanisms of opioids and the somatostatin analogue octreotide in cholera toxin-induced small intestinal secretion in the rat. The antisecretory effect of morphine and the somatostatin analogue octreotide was studied on cholera toxin-induced secretion in anaesthetized rats. Small intestinal secretion was induced with cholera toxin. Morphine (6 mg/kg b.wt.) and the somatostatin analogue octreotide (3 micrograms/kg b.wt.) reduced the cholera secretion in rats whose intestines had been subjected to sympathetic denervation. This was in contrast to the secretion elicited by helodermin which was unaffected by octreotide and morphine in the presence of nicotinic ganglionic blockade. The alpha-adrenergic receptor blocker phentolamine (1-2 mg/kg b.wt. i.v.) and the inhibitor of sympathetic transmitter release guanethidine (5 mg/kg b.wt. i.v.) abolished the antisecretory effect of morphine on the cholera secretion in contrast to the antisecretory effect of somatostatin which was unaffected by the alpha-blockade. It is proposed that the antisecretory effect of morphine and octreotide on cholera toxin-induced secretion was conducted at a step prior to the activation of the secretory epithelium and that the antisecretory effect of morphine was mediated indirectly by interaction with sympathetic nerve terminals in the intestine. The findings are consistent with a model where octreotide and morphine inhibit the nervous secreto-motor reflex activated by the cholera toxin.


Helospectin-like immunoreactivity in the esophagus. Helospectin I and II are two non-amidated, VIP-like peptides, isolated from the salivary gland venom of the lizard Heloderma horridum. The lower esophagus of cat, sheep and man was analyzed for helospectin-like immunoreactivity. Immunocytochemistry revealed helospectin-immunoreactive nerve fibers in the muscle layers, submucosa and mucosa of all species studied. In myenteric ganglia helospectin-immunoreactive nerve fibers and nerve cell bodies could be seen. Double immunostaining for helospectin and vasoactive intestinal peptide (VIP) revealed their coexistence in nerve fibers and cell bodies throughout the lower esophagus of all species tested. Double immunostaining for helospectin and neuropeptide Y revealed their coexistence in nerve fibres surrounding vascular and non-vascular smooth muscle. In the cat and sheep (but not in man) a subpopulation of the helospectin/VIP-containing fibers stored, in addition, substance P. The helospectin-immunoreactive material in the esophagus probably constitutes a novel neuropeptide. The distribution of the VIP/helospectin-immunoreactive neurons and fibers indicates their possible involvement in the regulation of motor and secretory activities.


Bivariate assay for cleaved atrial natriuretic factor (ANF(101-105/106-126)) in sheep plasma. A bivariate assay has been developed to measure both ANF, and cleaved ANF (ANF(101-105/106-126)) the primary product of endopeptidase-24.11 action on rat ANF(101-126). The assay employed two different antisera directed to the carboxy-terminal and ring regions of ANF to enable discrimination and measurement of intact endogenous ANF(99-126) and infused cleaved ANF (rat ANF(101-105/106-126)) in sheep plasma extracts. The assay which was validated by HPLC analysis of plasma extracts, had sufficient accuracy and precision to measure the metabolic clearance rate and half-life of cleaved ANF when infused in normal sheep.


Molecular cloning, sequence analysis and translation of proenkephalin mRNA from rat heart. Proenkephalin mRNA is abundant in rat cardiac ventricles but surprisingly low levels of opioid peptides or precursor forms derived from proenkephalin are present in tissue extracts. Proenkephalin mRNA in rat heart was characterized at the molecular level with the use of cDNA sequencing, in vitro translation, and primer extension. Two positive proenkephalin cDNA clones were obtained by screening approx. 20,000 recombinant phages from a heart cDNA library. Sequence analysis of the cDNA clones indicated that the heart transcript was the same form as in rat brain, but differed from the germ cell-specific testis transcript that utilizes a different transcriptional start site. Heart proenkephalin cRNA translated efficiently, resulting in the synthesis of a 35 kDa protein that was immunoprecipitated by an antibody specific to the protein. The transcriptional initiation sites utilized in the heart were the same as in the brain, based on primer extension studies. These data suggest that the proenkephalin transcript found in abundance in rat heart is the same form as found in the brain, and differs from the testis-type transcript. We conclude that the scant level of proenkephalin-derived peptides in the heart is not due to an intrinsic inability of the proenkephalin transcript to translate.


Discovery of a distinct binding site for angiotensin II (3-8), a putative angiotensin IV receptor. We report here the discovery of a unique and novel angiotensin binding site and peptide system based upon the C-terminal 3-8 hexapeptide fragment of angiotensin II (NH3(+)-Val-Tyr-Ile-His-Pro-Phe-COO-) (AII(3-8) (AIV)). This fragment binds saturably, reversibly, specifically, and with high affinity to membrane-binding sites in a variety of tissues and from many species. The binding site is pharmacologically distinct from the classic angiotensin receptors (AT1 or AT2) displaying low affinity for the known agonists (AII and AIII) and antagonist (Sar1,Ile8-AII). Although a definitive function has not been assigned to this system in many of the tissues in which it resides, AIV's interaction with endothelial cells may involve a role in endothelial cell-dependent vasodilation. Consequent to this action, AIV is a potent stimulator of renal cortical blood flow.


Role of cholecystokinin in mediating GRP-stimulated gastric, biliary and pancreatic functions in man. To explore the mechanisms of gastrin-releasing peptide (GRP)-induced gut functions in man, we investigated the effect on gallbladder contraction, exocrine pancreatic secretion and gastric acid secretion of a recently developed CCK receptor antagonist, loxiglumide, on GRP-stimulated effects in six healthy human subjects. Intravenous infusion of graded doses of synthetic human GRP (1-27 pmol/kg per h) caused significant and dose-dependent increases in pancreatic enzyme and gastric acid secretions and in gallbladder contraction. Intravenous administration of loxiglumide (10 mg/kg per h) abolished GRP-stimulated gallbladder contraction, augmented gastric acid secretion, but did not affect exocrine pancreatic secretion. The results suggest that endogenously released CCK is (1) responsible for GRP-stimulated gallbladder contraction, and (2) involved in regulating gastric acid secretion. The results further suggest that GRP-stimulated pancreatic secretion is not mediated by CCK, but has a direct response of GRP on the exocrine pancreas.


Measurement of T-kinin in rat plasma using a specific radioimmunoassay. T-kinin (Ile-Ser-Bradykinin) has been isolated only from the plasma of the rat and it is unclear whether the peptide, or its biosynthetic precursor, T-kininogen, circulates in the human. An NH2-terminally directed antiserum to T-kinin was raised in rabbits using an immunogen prepared by coupling the free -SH group of T-kinin extended from its COOH-terminus by a cysteinyl residue to an -NH2 group on human serum albumin. A radioimmunoassay was developed using this antiserum and 125I-labelled [Tyr10]T-kinin as tracer that was sensitive (least-detectable concentration 3 fmol/tube) and relatively specific for T-kinin (cross-reactivity with bradykinin and kallidin less than 1%). Treatment of rat plasma with an excess of trypsin in the presence of a kininase inhibitor generated T-kinin immunoreactivity equivalent to 455 +/- 71 pmol/ml (mean +/- S.E.M.; n = 9) and this immunoreactivity was eluted from a reversed-phase HPLC column as a single peak with the same retention time as synthetic T-kinin. In contrast, treatment of plasma from healthy human subjects (n = 8) and from patients (n = 8) with inflammation due to acute or chronic gastrointestinal disease under the same conditions did not generate any detectable T-kinin immunoreactivity. It is concluded, therefore, that T-kininogen, the biosynthetic precursor of T-kinin in the rat, is either absent from the plasma of human subjects or is present in a concentration less than 30 fmol/ml. Similarly, T-kininogen is probably not an acute phase reactant in humans.


Direct effect of bombesin on pancreatic and gastric growth in suckling rats. Bombesin stimulates growth of the stomach and pancreas in adult rats. Part of this effect is thought to be through the release of CCK following bombesin treatment. We studied the effect of long term administration of bombesin on the pancreas and stomach in suckling rats and examined the action of bombesin using specific CCK antagonist (CR-1409) and bombesin antagonists (GRP19-26, D-Phe19, Leu26CH2NHCOCH3 = cpd 17; L-686,095-001C002 = cpd 23). Rat pups (7-days-old) were given bombesin (20 micrograms/kg body wt. twice a day) or vehicle (1% gelatin) for 9 days. Bombesin stimulated pancreatic and gastric growth (tissue weight, total protein and DNA content all increased). Pancreatic trypsinogen concentration and content showed a 2-3-fold increase. CR-1409 at 6 mg/kg body wt., a dose that blocked the trophic action of CCK-33 when given to pups at similar ages, did not affect the bombesin-stimulated growth of the pancreas or the increase in trypsinogen level. At 2.4 mg/kg body wt., cpd 17 partially blocked and cpd 23 completely blocked the trophic effect of bombesin on the pancreas and stomach and the increase in trypsinogen level in the pancreas. RU-486, a type II glucocorticoid receptor antagonist, given at a dose sufficient to block the physiological action of glucocorticoid, had no effect on bombesin-stimulated growth of the pancreas. Thus, in vivo, bombesin acts directly on the neonatal pancreas and stomach.


Effects of atrial natriuretic factor on norepinephrine release in the rat hypothalamus. The effects of atrial natriuretic factor on the mechanisms involved in norepinephrine release were studied 'in vitro' in slices of Wistar rat hypothalamus. Atrial natriuretic factor (10, 50 and 100 nM) decreased spontaneous [3H]norepinephrine secretion in a concentration dependent way. In addition, the peptide (10 nM) also reduced acetylcholine induced output of norepinephrine. The atrial factor (10 nM) was unable to alter the amine secretion when the incubation medium was deprived of calcium or when a calcium channel blocker such as diltiazem (100 microM) was added. In conclusion, atrial natriuretic factor reduced both spontaneous and acetylcholine evoked [3H]norepinephrine release in the rat hypothalamus. These findings suggest that the atrial natriuretic factor may alter catecholamine secretion by modifying the calcium available for the exocytotic process of catecholamine output.


High potency of a new bombesin antagonist (RC-3095) in inhibiting serum gastrin levels; comparison of different routes of administration. This study was performed to evaluate the efficacy and duration of action of a new bombesin antagonist D-Tpi6,Leu13 psi (CH2NH)Leu14-bombesin (6-14) (RC-3095), given by different routes of administration, in suppressing gastrin releasing-peptide (GRP(14-27))-stimulated gastrin release in rats. First, we showed that GRP(14-27) itself was highly active when administered by different routes. GRP(14-27), given to rats at a dose of 25 micrograms/100 g b.w. significantly increased serum gastrin levels 3 and 6 min after intravenous and for more than 30 min after subcutaneous administration or pulmonary inhalation. RC-3095 was then injected subcutaneously, intravenously and also delivered by pulmonary inhalation at a dose of 10 micrograms/100 g b.w. in each case to seven male rats 2, 30, 60 or 120 min prior to i.v. administration of 5 micrograms GRP(14-27). RC-3095 administered 2 min prior to GRP(14-27) decreased the gastrin response to GRP(14-27), measured as area under the curve, by 81% in the intravenously injected group and 64% in the pulmonary inhalation group in the first 6 min. When GRP(14-27), was given 30 min after administration of RC-3095, the gastrin response was decreased by 52% in the subcutaneous group, 49% in the pulmonary inhalation group and 11% in the intravenous group during the first 6 min. RC-3095 delivered subcutaneously or by pulmonary inhalation 1 h before GRP(14-27) was also able to significantly inhibit gastrin release. Analysis of the data revealed that the bioavailability of RC-3095 given by the pulmonary inhalation route was about 69% of the s.c. route.(ABSTRACT TRUNCATED AT 250 WORDS)


Localization of calbindin D28K-like immunoreactivity in fish gill: a light microscopic and immunoelectron histochemical study. The presence of calbindin D28K in fish (Heteropneustes fossilis) gill was studied by use of specific antibodies raised against chick duodenal 28 kDa calbindin in immunoperoxidase and electron-microscopic labelling experiments. Immunoreactivity for calbindin D28K, which has been observed in the intestine of a number of avian and mammalian species, is reported for the first time in the gill. It was primarily located in neuroendocrine (NE) cells. Some immunoreactivity was also located in the glycocalyx of the non-endocrine cells, i.e., the pavement cells, which have ultrastructural characteristics quite different from those of endocrine cells. The calbindin-immunopositive NE cells were ascertained in both gill filamental and lamellar epithelium. All the NE cells contained secretory granules as the most distinctive feature of these cells. Ultrastructurally, two types of NE cells were distinguished according to the morphology of their secretory granules. The calbindin immunoreactivity in the NE cells was stimulated when the calcium concentration of the ambient water was reduced. The present findings suggest that NE cells exert some as yet unidentified function related to calcium-mediated processes involving the expression of calbindin.


Desmethylimipramine pretreatment prevents 6-hydroxydopamine induced somatostatin receptor reduction in the rat hippocampus. Several studies have shown anatomical and functional interconnections between catecholaminergic and somatostatinergic systems. To assess whether somatostatin (SS) may act presynaptically on catecholamine neurons, SS receptors were measured using radioligand test-tube binding assays on synaptosomes from hippocampus and frontoparietal cortex--areas that are innervated by catecholaminergic neurons with different densities and that have a high number of SS receptors--from control and 6-hydroxydopamine (6-OHDA)-treated rats. Intracerebroventricular (i.c.v.) injection of the catecholamine neurotoxin 6-OHDA (0.78 mg free base/kg of body weight in saline with 0.1% ascorbic acid) lowered hippocampal and frontoparietal cortical noradrenaline (NA) and dopamine (DA) levels at 1 week following the injection. Pretreatment of rats with desmethylimipramine (DMI) (40 mg/kg, intraperitoneal) prevented the drop in NA levels, but was not effective in attenuating DA depletion in the two brain areas studied. Treatment with 6-OHDA lowered the number of 125I-Tyr11-SS receptors in the hippocampus (130 +/- 19 vs. 266 +/- 16 fmol/mg protein, P < 0.001), whereas in the frontoparietal cortex a non significant 20% reduction in receptor number was found. The dissociation constants of 125I-Tyr11-SS binding to synaptosomes from frontoparietal cortex (0.65 +/- 0.06 vs. 0.60 +/- 0.04, P not significant) and hippocampus (0.44 +/- 0.04 vs. 0.63 +/- 0.14, P not significant) were similar in control and treated groups. Pretreatment with DMI reversed up to 80% of the effect of 6-OHDA on hippocampus SS receptors. DMI alone had no observable effect on the number and affinity of SS receptors. The 6-OHDA and the DMI treatment did not affect SLI levels in the brain areas studied. These results suggest that a portion of the hippocampal SS receptors may be localized presynaptically on the noradrenergic and dopaminergic nerve terminals.


Adrenalectomy does not change CRF secretion induced by interleukin-1 from rat perifused hypothalami. Interleukin-1 (IL-1) is a potent hypothalamic-pituitary-adrenal (H-P-A) axis activator. The hypothalamus is considered one of the main sites of action of IL-1 on the H-P-A axis, inducing CRF secretion, which is modulated by glucocorticoids. Glucocorticoids, which modulate CRF release by a negative feedback inhibition, have been postulated to exert a permissive action on the IL-1 effect on CRF secretion. Using a continuous perifusion system of rat hypothalami, the results of the present study indicate that at the same concentrations, IL-1 beta exerted a more potent effect than IL-1 alpha stimulating CRF secretion. The increase in hypothalamic CRF release induced by IL-1 was rapidly inhibited by both dexamethasone and corticosterone. However, adrenalectomy 2 or 8 days before did not modify CRF secretion induced by IL-1 from the in vitro perifused hypothalami. These data indicate that IL-1 does not seem to induce CRF secretion by interfering with an impeding action of glucocorticoids, although the cytokine effect is negatively modulated by corticosteroids.


Endogenous CCK is not involved in the regulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs. In this study, we assessed whether endogenous CCK is involved in the regulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs with force transducers chronically implanted in the gastric antrum, duodenum, jejunum and gallbladder. L364718 at a dose of 1.0 mg/kg was used as a specific and potent CCK receptor blocker, and its effect on spontaneous interdigestive motility and plasma motilin release were examined. Additionally, the contractile activity of exogenous synthetic canine motilin (20-100 ng/kg) with or without pretreatment with L364718 at a dose of 1.0 mg/kg was assessed. Whether the blocking effect of L364718 on CCK receptors was sufficient or not was verified by giving CCK-OP at a bolus dose of 10 ng/kg. As a result, cyclic changes in interdigestive motor activity and the plasma motilin concentration were not affected by pretreatment with L364718. L364718 also did not affect motilin-induced interdigestive contractile activity in the gastrointestinal tract and gallbladder. On the other hand, the effect of CCK-OP was completely abolished by pretreatment with L364718. It is concluded that endogenous CCK is not involved in the regulation of spontaneous and motilin-induced interdigestive contractions in the canine gastrointestinal tract and gallbladder.


Codex Committee on Pesticide Residues--a plan for improved participation by governments. The Codex Committee on Pesticide Residues (CCPR), which is responsible for establishing maximum residue limits (MRLs) for pesticides on food, has a vital role in protecting the public health and facilitating international trade. Codex MRLs are based on scientific evaluations by expert panels that constitute the Joint FAO/WHO Meeting on Pesticide Residues (JMPR). These panelists estimate an acceptable daily intake for a pesticide and expected level of residue remaining in food when the pesticide is used according to good agricultural practice. The goals of the CCPR are not being fully achieved. Governments are generally not accepting Codex MRLs; instead, technical and procedural aspects of the JMPR and CCPR process are being criticized. The CCPR is responding to valid criticisms of the process; however, governments may still lack the will to seek harmonization of pesticide limits for food in international trade. Overcoming this problem will be difficult, but not impossible. A plan of action is proposed that allows countries to selectively accept Codex MRLs, increase the number of chemicals in the JMPR/CCPR system for evaluation, and be responsive to both their consumers and their food producers without compromising national health and safety standards and competitive trade advantages.


Perspectives on formaldehyde toxicity: separating fact from fantasy. Formaldehyde (IUPAC name, methanal) is one of the simplest, most ubiquitous molecules in our environment and troposphere. Exposure to large amounts of formaldehyde can produce a variety of respiratory and dermatologic problems in humans, in both the home and the workplace. However, in spite of anecdotal reports on formaldehyde-induced illness over the past 20 years there is a paucity of data regarding its potential as either an allergen or an antigen in humans. In addition, many of our current impressions about formaldehyde are based on studies of dubious scientific validity. In this review, we discuss the biological and chemical properties of formaldehyde and its presence in materials which we come in contact with, and finally attempt to put in perspective our current understanding of the detrimental effects of formaldehyde on our health, or lack thereof. There is no evidence at present that formaldehyde causes immunological diseases. Finally, and unfortunately, many of the studies have drawn invalid conclusions and are based on poorly controlled anecdotal observations.


An alternative to the USEPA's proposed inhalation reference concentrations for hexavalent and trivalent chromium. The passage of the Clean Air Act Amendment of 1990 reflects a growing public concern over human exposure to air toxics. The EPA is currently identifying inhalation reference concentrations (RfCs) to be used as risk criteria for determining whether existing or predicted ambient levels of chemicals are above acceptable concentrations. This paper evaluates the risk assessment methods used by the EPA to develop the recently proposed RfC (0.002 micrograms/m3) for both trivalent chromium [Cr(III)] and hexavalent chromium [Cr(VI)]. Based on our evaluation, these RfC values do not appear to have been developed in accordance with standard Agency procedures or classic toxicology methods for setting RfCs. In particular, the "key" study used by the EPA [E. Lindberg and G. Hedenstierna (1983) Arch. Environ. Health 38, 367-374] as the basis for their proposal is not appropriate because it examined only the effects of exposure to chromic acid mist [Cr(VI)], even though most environmental exposure is to Cr(VI) and Cr(III) as a dust. The health hazards of Cr(VI) as an acid mist are significantly different from those associated with Cr(VI) as a dust. Further, the EPA's key study did not evaluate exposure to Cr(III), the toxicity of which is significantly different from both particulate Cr(VI) and chromic acid mist. Finally, the uncertainty factors used to account for data gaps were unusually high, thus providing RfC values equal to or below most naturally occurring environmental levels and standard analytical limits of detection. In this paper, we propose alternative RfCs for Cr(VI) as chromic acid mist and for Cr(VI) as a dust. Based on the Lindberg and Hedenstierna study, we derived an RfC of approximately 0.12 micrograms/m3 for chromic acid mist. An RfC of 1.2 micrograms/m3 is recommended for particulate Cr(VI) based on animal studies that evaluate long-term inhalation exposure to Cr(VI) dust. Due to its low toxicity, an RfC for Cr(III) is not warranted.


Thyroid follicular cell carcinogenesis: results from 343 2-year carcinogenicity studies conducted by the NCI/NTP. The National Toxicology Program data base on 343 mouse and rat carcinogenesis studies was reviewed to determine the frequency of and relationship between hyperplastic and neoplastic follicular lesions of the thyroid gland. The frequency of chemically related lesions in the thyroid was also compared to neoplastic lesions in the liver to investigate a possible correlation. The percentage of studies observed to have positive or equivocal chemically related thyroid proliferative lesions was rats: male, 14%, female, 11%; mice; male, 8%; female, 9%. When positive in one sex for a given chemical, there was a 60-80% chance of it being positive in the other sex of the same species, although interspecies correlation was not as strong. Thyroid follicular cell neoplasia without hyperplasia was uncommon in mice but was common in rats. Chemicals that caused thyroid proliferative changes were more likely (P less than 0.05) to produce liver neoplasms (both within and between species) than were chemicals causing no thyroid changes. However, this correlation was far from perfect, with many chemicals producing thyroid proliferative lesions, but not liver neoplasms and vice versa. This suggests that universal correlations are not supportable by the data and that individual chemicals should be evaluated on a case-by-case basis.


Role of maternal toxicity in assessing developmental toxicity in animals: a discussion. The belief that any drug or chemical, when administered at a high enough dose, can be expected to produce fetal malformations is not consistent with the facts. However, the stress associated with maternally toxic doses can be expected to result in associated, often transient, fetal abnormalities that may not be the result of deviant organogenesis. Sometimes the toxicity toward the pregnant animal, including her embryos/fetuses since they are hardly in a sanctuary, is severe enough to result in resorption of the embryo or abortion of the fetus. Thus, it is possible that the embryolethality and other indications of developmental toxicity, produced by some drugs and chemicals, may be the result of a mechanism(s) other than selective toxicity toward the embryo. Also, some test materials have been shown to affect maternal homeostasis, thereby disrupting support to the embryo, without causing significant overt toxicity to the embryo or dam; e.g., the endocrine system of the dam is altered. Routine testing has thus far revealed a relatively limited number of true teratogens, although a large number of drugs and chemicals have resulted in fetal effects such as developmental variations when administered at doses that approach lethal levels. Such effects on the fetus should be expected when the maternal animals are stressed by the high dosages usually employed. A better understanding of the etiology and biological relevance of the embryo/fetal deviations often seen in developmental toxicology studies might help to avoid the sometimes unjustified withholding of potentially useful drugs and chemicals from the marketplace.


An analysis of the U.S. Environmental Protection Agency neurotoxicity testing guidelines. Few of the more than 65,000 chemicals listed in the Environmental Protection Agency (EPA) inventory have been tested for neurotoxicity. The nervous system may be especially vulnerable to toxicants because many compounds can cross the blood-brain barrier and induce irreversible damage. Additionally, the young, the elderly, and other sensitive populations may be particularly susceptible to neurotoxic injury. The EPA has developed guidelines including neurobehavioral, neuropathological, and neurochemical tests for the identification of possible neurotoxicants. In the present review, tests included in the current EPA guidelines for neurotoxicity testing are described and evaluated. The main benefit of the tests is that regulators are familiar with them, thus facilitating interpretation. Additionally, validation data on these tests are available for many known neurotoxicants. These factors make it difficult to introduce new methods that may include in vitro and other techniques. The current in vivo tests can be costly and prolonged and can involve the use of many laboratory animals, making them inappropriate for generalized use on existing chemicals. It is suggested that alternative tests be incorporated for screening of large numbers of chemicals and that testing priority be given to chemicals on the basis of structure/activity relationships, lipophilicity, bioaccumulation, and extent of exposure.


[The significance of the AMES and the NTM systems to determine the prognosis in patients with differentiated cancer of the thyroid]. The author considers that the AMES and TNM systems are reliable in determining the prognosis in patients with well differentiated thyroid carcinoma. In low risk patients with tumors less than 2 cm in diameter, total lobectomy and hormonal suppression are sufficient therapy. In other patients, total or subtotal thyroidectomy are advisable to facilitate further control and therapy. Total or subtotal thyroidectomy should always be done in high risk patients. Metastases to the regional lymph nodes are not an important risk factor, but they should always be excised. Radioactive iodine therapy is not useful for low risk patients.


[Cloning of kDNA minicircles in different species of Leishmania and its use as probes for diagnosis]. The present study describes the cloning procedure for fragments of kinetoplast DNA minicircles from different Leishmania species and its use for detecting the presence of these parasites. Our methodology was as follow: the DNA of the kinetoplast from Leishmania mexicana amazonensis and Leishmania braziliensis panamensis was extracted, purified and digested with the enzyme Dra I. These fragments were cloned in the site for Hinc II in the plasmid pKS. E. coli was the bacterial strain used for transforming and amplifying the cloned fragments; the selection was carried out in LB medium supplemented with ampicillin. With the clones suspected to be positives we run a Southern blot and total kDNA, from each Leishmania species, was used as hybridization probe. Finally, the cloned purified fragments were tested as diagnostic probes against kDNA from eleven different species of Leishmania and one of Trypanosoma cruzi parasites. After cloning, transforming, amplifying and selecting, we obtained two probes of fragments of kDNA minicircles: one from L. m. amazonensis and the other from L. b. panamensis. Both probes showed high sensitivity for diagnosing cutaneous Leishmania complexes (Mexicana or Braziliensis); however, we observed a low grade crossreaction between some species belonging to the same complex. It is necessary to continue studies in order to obtain subfragments of these probes with a higher grade of specificity at the level of species and subspecies.


[Fetal cardiocirculatory physiology].

[Fetal cardiocirculatory physiology]. The authors analyzed the physiology of fetal circulation and its variations during hypoxia. They propose a systematic approach which would allow early diagnosis of hypoxia during its initial phases, as a contribution in order to reduce perinatal morbidity and mortality.


["Cholos de Coclé": determination of their racial mixture and genetic origins]. We have found, in this first genetic study of a supposedly admixed Panamanian population, that the cultural group known as "cholos of Coclé" constitute a trihybrid mixture, whose genetic pool has the following composition: 44% Amerindian, 38% Caucasoid and 18% Negroid. Similarly, we have detected Amerindian genes, such as LDHB--Gua and TFchi, in proportions that relate this population with the extant Ngawbé (Guaymí). Nevertheless, the very high frequency of variant PEPA--KUN seems to indicate the genetic contribution of Amerindian populations from Eastern Panama, possibly from the extinct indigenous group cueva. This variant is frequently found among the present-day Kuna, but has not been detected among Nagawbé and Buglé.


[Laparoscopic pelvic lymphadenectomy in patients with cancer of the prostate]. Laparoscopic pelvic lymphadenectomy is a new procedure to determine the propagation grade of Prostatic adenoma and the treatment to recommend. It is a satisfactory procedure for the diagnosis, with minimal morbidity. It is described our early experience in Panama, 6 patients and 51 lymph nodes removed.


[Acute epiglottitis in adults].

[Acute epiglottitis in adults]. The author presents the clinical history of 14 patients, from 21 to 48 years of age, 10 men and 4 women, with a final diagnosis of acute epiglottitis who were hospitalized at Gorgas Army Hospital or at the San Fernando Clinic. All the patients had pharyngitis and dysphagia, a few with nasal voice, stridor and difficulty breathing, as the chief complaint. All the patients were initially intubated orally for diagnostic purposes and immediately after nasotracheal intubation was done until the patient improved in 2 or 3 days (one patient remained intubated for 5 days). All patients were kept in the Intensive Care Unit and were treated with Ampicillin and Chloramphenicol IV and lately with a second generation cephalosporin (Cefamandole). The patients allergic to Penicillin were treated with Clindamycin and Chloramphenicol. Corticosteroids were not used in any of the patients. There were no sequelae and none of the patients expired.


[Changes in the pain produced by the peripheral venous injection of propofol when it is combined with lidocaine or fentanyl]. The author studied the use of intravenous Propofol for the relief of pain. He demonstrated that Propofol and 10 mg of Lidocaine intravenously decreased moderate or severe pain from 31.6% to 9% and that increasing the dose of Lidocaine did not significantly decrease the pain further. Fentanyl did not produce a statistically significant further diminution of the pain from the level of relief obtained with Propofol.


[Prevalence of Helicobacter pylori in patients with gastric cancer in Panama]. Cancer of the stomach is the second in incidence in Panama after the cancer of the prostata. It is studied now the incidence of infection due to Helicobacter pylori in patients with gastric carcinoma. It seems to be a significative relationship between the prevalence of gastric carcinoma and H. pylori infections. This observation is important because by the similar therapeutic implications in virus DNA hepatitis type B and hepatoma.


[Isolation and identification of Gardnerella vaginalis in women with symptoms of bacterial vaginosis]. 70 samples of vaginal secretions were collected from women with bacterial vaginosis syndrome, that were attended in Nuevo Veranillo' Health Center. All samples were tested in order to determinate the presence of amine and to Gram'methods stain to observe the morphologic characteristics of the "Clue" cells (epithelial cells with adhered bacteria). Samples were cultured in a selective media of blood agar in Columbia base with colistine and nalidixic acid, and incubated in an environment of CO2 at 37 degrees C. Tests of oxidase, catalase, glucid fermentation, hippurate hydrolysis and starch hydrolysis were made on the grown colonies. 27 out of 70 samples resulted in positive cultures for Gardnerella vaginalis, 11 to pregnant women and 16 to nonpregnant women; among these, 14 women used some kind of contraceptive methods as DIU or pill.


[The propedeutic course given at the School of Medicine and the academic performance of the students that passed it]. A report of the results of the Propedeutic Course in the Medical School of the University of Panama is informed. This course was established by the Academic Council, at the request of the Medical School, to diminish the registration form 280 to 180 students, taking into account the low academic performance of the students with the lowest grades in the Admission Process. The study showed that the correlation indices of the students in the Propedeutic Course and in the first regular semester was low. The study also showed that the number of students from the Propedeutic Course who repeated or were separated from the school, was higher than those from the regular semester.


Neoplastic and inflammatory processes of the peritoneum, omentum, and mesentery: diagnosis with CT. Disease processes in the peritoneum, omentum, and mesentery occasionally are not recognized at radiologic examination. The authors have used computed tomography (CT) to categorize the radiologic appearances of the more common abnormalities into three basic patterns: (a) solid but relatively well-defined masses, (b) cystic-appearing masses, and (c) ill-defined or infiltrative processes. The most common solid masses to affect these anatomic regions are secondary neoplasms, which are associated with enhancement of the peritoneum on contrast material-enhanced CT scans and, typically, ascites. The various cystic-appearing masses (including cystic lymphangioma, cystic mesothelioma, teratoma, and loculated ascites) and infiltrating masses (such as peritoneal mesothelioma, retractile mesenteritis, desmoid, and carcinoid) must be differentiated on the basis of clinical findings and additional imaging findings (eg, CT depiction of fat and calcium in teratomas and the radiating appearance of carcinoids). Although the CT appearances of some of the abnormalities overlap, classifying them by pattern is helpful in narrowing the range of the differential diagnosis.


Clinical significance of pneumatosis of the bowel wall. The presence of gas within the bowel wall is an uncommon condition that is typically first diagnosed by the radiologist. Although it is often seen on abdominal radiographs, computed tomography is more sensitive in demonstrating pneumatosis and its complications. There is a spectrum of disease states that produce this abnormality, ranging from the innocuous to the fatal. Its radiographic appearance is variable, particularly the location, extent, severity, and presence of pneumoperitoneum or portal venous gas. None of these imaging characteristics can be considered pathognomonic for the underlying cause of the pneumatosis. The radiologist must be aware of the different conditions associated with this entity, as well as their variable appearances.


MR imaging of posterior fossa infarctions: vascular territories and clinical correlates. Ischemic infarctions in certain vascular territories of the cerebellum and brain stem can produce some characteristic radiologic and clinical patterns. The cerebellum serves as a coordination center for the maintenance of equilibrium and muscle tone and refines the movements of the somatic muscles. The anatomy of the brain stem is extremely complex, and small infarcts can potentially be disastrous. MR imaging depicts the anatomy of the posterior fossa and infarcts in this region with greater accuracy than was previously possible. Familiarity with the vascular territories and patterns of infarction of the posterior fossa depicted with MR imaging and familiarity with the associated clinical symptoms of stroke in this region can help the radiologist recognize these infarcts and correlate clinical and radiologic findings. When patients are referred for MR imaging of the brain because of clinical findings suggestive of infarction, it may be useful to obtain coronal or sagittal views in addition to axial images to better depict the vascular distribution of a suspected ischemic lesion.


Gadolinium-enhanced MR imaging of renal masses. Preliminary reports indicate that gadolinium-enhanced magnetic resonance (MR) imaging is highly accurate for diagnosis of renal masses. The authors demonstrate the clinical utility of MR imaging for evaluating renal masses in 26 patients for whom contrast material-enhanced computed tomography (CT) was contraindicated or inadequate for diagnosis or staging. Nine patients had complex cysts, one had a perinephric hematoma, and 16 had a solid mass (three of which were benign). All patients underwent MR imaging before and after administration of gadopentetate dimeglumine. Multiple imaging techniques and sequences were used. All tumors and no cysts enhanced with gadolinium. Even though the three benign tumors enhanced, two were differentiated from renal carcinoma on the basis of other imaging features. Unenhanced MR imaging was accurate in staging of renal carcinomas, and use of gadolinium did not improve staging accuracy. Gadolinium-enhanced MR imaging is indicated when results of CT and sonography are indeterminate for malignancy and when contrast-enhanced CT is contraindicated because of renal failure or adverse reaction to iodinated contrast material. In this latter instance, MR imaging is useful for both diagnosis and staging.


Misleading aggressive MR imaging appearance of some benign musculoskeletal lesions. After plain radiography has been performed, magnetic resonance (MR) imaging is considered the modality of choice for the evaluation of suspected musculoskeletal lesions because of its exquisite sensitivity to changes in the signal intensity of marrow and soft tissue. That sensitivity, however, may lead to an overestimation of the aggressiveness and extent of some benign bone lesions, particularly in children. Such lesions include chondroblastoma, osteoid osteoma, eosinophilic granuloma, and stress fractures. Potentially misleading MR features commonly seen include prominent marrow edema, soft-tissue edema, and apparent mass effect adjacent to the bone lesion. Features that these lesions have in common that may explain the MR findings include associated inflammatory reactions caused by the lesions and their occurrence in childhood, when the periosteum is more loosely attached. Knowledge of the potential pitfalls encountered with MR imaging may help explain the discrepancy between the radiographic and MR appearances of these benign lesions and avoid misplaced reliance on MR imaging for a diagnosis. Radiography remains the single most valuable modality in determining a differential diagnosis for bone lesions.


Effect of poor control of film processors on mammographic image quality. With the increasingly stringent standards of image quality in mammography, film processor quality control is especially important. Current methods are not sufficient for ensuring good processing. The authors used a sensitometer and densitometer system to evaluate the performance of 22 processors at 16 mammographic facilities. Standard sensitometric values of two films were established, and processor performance was assessed for variations from these standards. Developer chemistry of each processor was analyzed and correlated with its sensitometric values. Ten processors were retested, and nine were found to be out of calibration. The developer components of hydroquinone, sulfites, bromide, and alkalinity varied the most, and low concentrations of hydroquinone were associated with lower average gradients at two facilities. Use of the sensitometer and densitometer system helps identify out-of-calibration processors, but further study is needed to correlate sensitometric values with developer component values. The authors believe that present quality control would be improved if sensitometric or other tests could be used to identify developer components that are out of calibration.


Receiver operating characteristic curves: a basic understanding. Receiver operating characteristic (ROC) is one form of an objective measurement that can be used to compare newer imaging technologies against human observer performance (the ability of the expert radiologist). Use of ROC curves allows one to account for a continuum of radiologic interpretations when calculating sensitivity and specificity for an imaging modality and avoids the inaccuracies that arise from assuming that imaging findings are absolutely normal or abnormal. An ROC curve is generated by plotting sensitivity on the y axis as a function of [1-specificity] on the x axis for a continuum of diagnostic criteria. ROC curves allow visual analysis of the trade offs between the sensitivity and the specificity of a test with regard to the variable diagnostic criteria used by radiologists. Because ROC curve analysis is gaining wide acceptance in medical literature, an explanation of ROC methods with the use of simple examples is necessary to increase the knowledge and understanding of practicing radiologists.


Congenital and acquired orthopedic abnormalities in patients with myelomeningocele. This article presents a radiologic review of the spectrum of acquired and congenital orthopedic abnormalities found in patients with myelomeningocele. These abnormalities are caused predominantly by muscle imbalance, paralysis, and decreased sensation in the lower extremity. Iatrogenic injury, such as a postoperative tethered cord, may also cause bone abnormalities. Selected images were obtained from more than 800 children. Important entities presented include spinal curvatures such as kyphosis, scoliosis, and lordosis; subluxation and dislocation of the hip, coxa valga, contractures of the hip, and femoral torsion; knee deformities; rotational abnormalities of the lower extremity and external and internal torsion; ankle and foot abnormalities such as ankle valgus, calcaneus foot, congenital vertical talus (rocker-bottom deformity), and talipes equinovarus; and metaphyseal, diaphyseal, and physeal fractures. Familiarity with congenital abnormalities and an understanding of the pathogenesis of acquired disorders in patients with myelomeningocele are essential for proper radiologic interpretation and timely therapy.


Congenital malformations of the cervicothoracic lymphatic system: embryology and pathogenesis. Familiarity with the embryology of the lymphatic system is helpful in understanding the pathogenesis and radiologic appearance of lymphangiomas of the cervicothoracic region. By considering anatomic location and radiologic appearance, one can predict the type of lymphangioma present, the primordial lymph sac from which the malformation arose, and when it formed in embryonic life. Cystic hygromas are composed of large, dilated lymphatic spaces. They form when a primordial lymph sac fails to reestablish communication with the central venous system from which it arose. These lesions may also result from an aberrant bud arising from a primordial lymph sac. Cavernous and capillary lymphangiomas are composed of smaller lymphatic channels. They form from abnormally sequestered buds of the developing lymphatic mesenchyme responsible for the fine meshwork of terminal branches in the periphery of the embryo. Their growth may be inhibited by the relatively tougher tissues in the periphery (eg, skin and muscle) compared with the relatively loose fatty connective tissue in which cystic hygromas form. Not only can all types of lymphangioma occur in one lesion, but lymphatic and vascular malformations may also coexist.


Imaging manifestations of pleural tumors. Although radiologic assessment of pleural tumors may be accomplished with several imaging modalities, the standard noninvasive techniques include chest radiography and computed tomography (CT). These examinations may be supplemented with magnetic resonance imaging and occasionally with ultrasound. Depending on the location, size, and underlying histologic features, pleural tumors may produce a spectrum of findings. CT is particularly useful in defining the location and extent of these masses. The authors present a review of basic pleural anatomy and imaging features of both benign and malignant pleural neoplasms. The pleural may be involved by one of several primary or metastatic tumors. Specific cell types are diffuse malignant mesothelioma (the most common plain radiographic findings are unilateral pleural effusion and pleural thickening), localized fibrous tumor (circumscribed, spherical or ovoid, noncalcified lesions arising in the pleural surface), metastatic disease (radiographic findings may mimic those of malignant mesothelioma), and uncommon neoplasms including thymoma and lymphoma. Among these various pleural tumors, metastatic disease represents the most common neoplasm.


From the archives of the AFIP. Leiomyosarcoma of the retroperitoneum and inferior vena cava: radiologic-pathologic correlation. Leiomyosarcoma is the second most common primary retroperitoneal tumor in adults. Retroperitoneal leiomyosarcoma exhibits three major growth patterns: (a) completely extravascular (extraluminal) (62% of cases), (b) completely intravascular (intraluminal) (5% of cases), and (c) extra- and intraluminal (33% of cases). The usual clinical manifestation is a large abdominal mass. Intraluminal leiomyosarcoma may be accompanied by symptoms referable to venous thrombosis. The variable gross features and potential for intravascular extension result in various radiologic appearances, the most common being a large, partially necrotic soft-tissue mass in the retroperitoneum with or without extension into the inferior vena cava. Computed tomography and magnetic resonance imaging typically show a nonfatty, necrotic retroperitoneal mass and a vascular component when it is present. Ultrasound and angiography may also be useful, especially if vascular involvement is suspected from other imaging studies. Treatment of choice is surgical excision, which is frequently impossible due to the invasiveness of the tumor. Prognosis is related to extent of invasion and the adequacy of resection. Long-term prognosis is poor, and most patients die of local recurrence or distant metastasis.


Radiation dose in CT.

Radiation dose in CT. The energy deposited in the patient by the rotating x-ray beam in computed tomography produces more uniform absorbed dose values within the section of imaged tissue than those produced in conventional radiologic procedures. The dose values within a specific section are determined by factors such as voltage, current, scan time, scan field, rotation angle, filtration, collimation, and section thickness and spacing. For routine dose determinations, a pencil ionization chamber is usually employed with a plastic phantom. Dose for a specific patient can be determined with thermoluminescent dosimeters placed on the patient. Multiple-scan procedures normally increase the dose in a specific section by less than a factor of two. Typical multiple-scan average doses are in the range of 40-60 mGy for head scans and 10-40 mGy for body scans. Integral dose, however, is directly proportional to the number of sections in an examination. When examination factors are changed to reduce dose, the image noise increases. An optimum protocol is one that results in a balance between dose and image quality.


[Coxa vara in children. Apropos of 28 cases]. Infantile coxa-vara is an infrequent lesion and two etiologic factors have been recognised: mechanical and genetic. As in Blount's disease, the same populations (black and scandinavian people) are usually affected. Twenty eight patients with 42 infantile coxa vara were reviewed. The diagnosis was often late. The radiographs showed the decrease of the neck-shaft angle and the signs of cervical dystrophy. The aggravation of the coxa vara is usual and pseudarthrosis or osteo-arthritis can be observed. Thirty six femoral valgus sub-trochanteric osteotomies were done. The results were best when the surgery was done before the age of 9 years. When the surgery was done later, an epiphysiodesis of the greater trochanter was associated to the femoral osteotomy if the epiphyseal cartilage was fused. Langenskiold's osteotomy was used only when the neck-shaft angle was lower than 80 degrees. The results were evaluated according to the neck shaft angle and the morphology of the femoral head: 22 very good and good, 11 fair and 3 bad results were noted.


[Arthroscopic internal meniscectomy in patients over 55 years of age. Results over more than 4 years]. Fifty-one meniscectomies by arthroscopy were realised on patients of more than 55 years of age between 1981 and 1986. Twenty-four patients were reviewed after at least 4 years of follow up, 12 of them after a 7.5 years follow up. 21 results were noted as functionally very good or good, 3 were poor. The radiological analysis of femoro-tibial compartments in comparison with the non operative side showed a clear pejorative difference in one case, moderate in 5 without incriminating the morphological type. If the quality of result does'nt correlate with age, it was'nt the same for the type of lesion seen during arthroscopy, the best results after arthroscopic meniscectomies were seen in traumatic lesions occurring on normal menisci or on degenerative ones. The authors concluded that medial meniscectomy in patients older than 55 years is justified in precise indications: a known traumatism or also acute medial pain, or speedy with normal or subnormal X-ray and after a positive arthrography.


[Hallux valgus: the McBride procedure or subcapital osteotomy?]. The authors compared the long term follow-up (mean duration 19 years) of 96 patients operated on for hallux valgus, 52 by the McBride procedure, 46 by a Hohmann procedure. Clinical results considered 4 criteria: deformity, pain, mobility and satisfaction. Dorsoplantar weight bearing X-ray compared anatomical results. This study showed that patients were subjectively more satisfied after McBride operation (p = 0.0001) even if the deformity was radiologically better reduced by osteotomy (p = 0.006). This discrepancy between subjective and radiologic results was related to the fact that X-rays represent only the static morphologic reflect of a more complex pathologic entity: radiology can only partly explain the functional discomfort of the patients. The modified McBride procedure was better suited to patients presenting a painful HV. Osteotomy was more suited to bunions causing little pain. Indications for each of these procedures should be based more on patient's history and clinical examination than on X-rays.


[Ulnar translocation of the carpus after surgery of the rheumatic wrist. Review of 54 cases]. Fifty-four rheumatoid wrists, on which synovectomy and caput ulnar resection had been performed, were re-examined 1 to 8 years after the operation (average follow-up: 3.8 years). The clinical results were good, and the wrists pain-free in 91 per cent of cases, with a low rate of synovitis recurrence (4 per cent), and 88 per cent of the mobility in the sagittal plane was preserved. Radiological examination revealed a moderate aggravation of carpite over the years. This evolution was not linked, however, to the fact that no intracarpal synovectomy was performed in our series since a similar evolution has been reported by authors who carry out this synovectomy. Ulnar translocation of the carpus was commonly measured in relation to the ulna axis, but as the latter tends to get into a more medial position after the surgery this analysis was incorrect. Ulnar translocation should be measured in relation to the axis of the radius, which remains in the same position. Studied in this way, the average translocation in this whole series was 2 mm. A comparative study of the operated wrist and the non-operated wrist in 27 patients revealed a significant aggravation (p < 0.2) of ulnar translocation of the carpus at radiological stages 2 and 3. This translocation remained however minimal. A combined transfer of the extensor carpi radialis brevis or longus onto the extensor carpi ulnaris did not slow down ulnar translocation of the carpus, but the other hand it improved the correction of radial deviation of the carpus and ulnar deviation of the fingers.


[Total denervation of the wrist. Apropos of 50 cases]. Fifty patients who underwent a total denervation of the wrist were reviewed after an average of 5 years post-operatively. The main aetiology was diffuse osteo-arthritis secondary to scaphoid nonunion (44 per cent) and Kienbock's disease, stage IV (22 per cent). This resulted in pain and functional disability. Another surgical procedure was carried out in 40 per cent of patients. Post-operative complications included one painful neuroma and 3 patients complained of radial nerve paraesthesia. Pain was improved in 36 of the 50 patients with an average score of 72 over a scale of 100. There was no significant change in power or range of movement.


[Bipolar endoprosthesis in fractures of the femoral neck. Apropos of 201 cases, 116 after a 6-year follow-up]. We report our experience with 201 SEM bipolar prostheses used to treat femoral neck fractures in patients with a mean age of 70 years and a mean follow-up of 57 months (median 75 months). Clinical outcome was favorable with 94 per cent satisfactory results (very good and good). Femoral complications requiring reoperation (conversion to total hip replacement) occurred in 2.2 per cent of cases. Among the 163 patients for whom roentgenographic data were available, 5 (3.6 per cent) developed evidence of acetabular wear but remained symptom-free and did not require reoperation. As compared with Moore's prosthesis, the SEM bipolar prosthesis seems to provide substantially better clinical and roentgenographic results. For the treatment of femoral neck fractures, total hip replacement seems to provide results comparable to those reported here but requires a more sophisticated operative technique and carries a greater risk of subsequent dislocation. Two factors prevent the widespread use of the bipolar prosthesis at present: the need for femoral grouting which carries a well-documented risk of hemodynamic complications, and the higher cost of the device.


[Embolization of the circumflex femoral artery for recurrent hemorrhage after total hip arthroplasty. Apropos of a case]. Reoperation of an haemorrhagic complication after total hip arthroplasty may be not efficacious when, as in the case report, bleeding's origin is not found. The vital prognosis can be quickly set in action and then the arterial embolization be the swift and efficacious solution. The selective arteriography that precedes it allows to locate the bleeding's origin, to estimate gravity of leak and to set indication of embolization. So it is fitting to think of this therapeutic solution that may avoid new operation and new failure.


[Necrotizing fasciitis of the upper limb: a case]. Necrotizing fasciitis is a rare form of anaerobic infection, quite different from gas forming gangrene: it affects the skin, the cellular tissue, the fascia; it doesn't diffuse in depth to the muscles and doesn't produce gas. Its microbic agents vary from haemolytic streptococcus to anaerobic bacteria in synergy. It rapidly spreads into a massive necrosis and can in a week's time lead to death by toxic shock. It spreads locally to large cutaneous areas eventually leading to the necessity of amputations. A joint treatment must be started with extreme urgency: extensive surgical excisions of all necrotic teguments, and medical treatment consisting of correcting metabolic troubles and antibiotherapy. This difficult treatment can save the patient, but it involves great loss of cutaneous and subcutaneous substance leading to local problems which are similar to serious burns, then to problems of reconstruction. An open fracture of the elbow led to an observation. A review of the literature sets out the different forms and complications.