Screening of newborn infants for cholestatic hepatobiliary disease. Does test fulfil screening criteria?
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Humans↗
Biomedical subjects
A Paul
Publications and source records attributed to A Paul.
[Hepatitis C. Saving the liver].
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Antiviral Agents↗
Reduced progression of atherosclerosis in apolipoprotein E-deficient mice with phenylhydrazine-induced anemia.
Epidemiological and experimental studies suggest that circulating erythrocytes play a role in the incidence of coronary heart disease. We investigated the influence of phenylhydrazine (PHZ)-induced anemia on the formation of atherosclerotic lesions in apo E-deficient mice on regular chow and on a high-fat, high-cholesterol diet during 10 weeks. The repeated doses of PHZ caused sustained anemia throughout the study, changes in the physical characteristics of erythrocytes and increased reticulocyte count. The lesions of the anemic animals were smaller than in the controls and this was even more evident in mice fed with the atherogenic diet. A positive correlation was found between circulating red blood cells at the end of the experiment and the area of aortic lesion. There was also a negative association between the lesion and the reticulocyte count. This reduced progression of atherosclerotic lesions is independent of nutritional status or the lipoprotein cholesterol distribution. The results suggest that mechanisms related to the number of circulating red blood cells may have a significant influence on the development of atherosclerosis.
Anemia↗
[Surgical robot in endoprosthetics. How CASPAR assists on the hip] the hip].
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Arthroplasty, Replacement, Hip↗
Regulation of electrogenic anion secretion in normal and cystic fibrosis gallbladder mucosa.
Fluid and ion transport across biliary epithelium contributes to bile flow. Alterations of this function may explain hepatobiliary complications in cystic fibrosis (CF). We investigated electrogenic anion transport across intact non-CF and CF human gallbladder mucosa in Ussing-type chambers. In non-CF tissues, baseline transmural potential difference (PD), short-circuit current (Isc), and resistance (R) were -2.2 +/- 0.3 mV (lumen negative), 40.7 +/- 7.8 microA/cm2, and 66.5 +/- 9.6 Omega. cm2, respectively (n = 14). The addition of forskolin (10(-5) mol/L) to the apical and basolateral baths and that of adenosine 5'-triphosphate (ATP) (10(-4) mol/L) to the apical bath induced significant increases in Isc by 8.0 +/- 1.4 and 10.3 +/- 1.8 microA/cm2, respectively. Depletion of bathing solutions in Cl- and HCO3- significantly reduced baseline Isc and the forskolin- and ATP-induced increases in Isc. Anion secretion was stimulated by extracellular ATP via P2Y2 purinoceptors, as indicated by the effects of different nucleotides on Isc and on 36Cl efflux in cultured gallbladder epithelial cells. This effect was mediated by cytosolic calcium increase and Ca2+/calmodulin-dependent protein kinase II, as ascertained by using inhibitors. In CF preparations, basal PD and Isc were lower than in non-CF, and the response to forskolin was abolished, whereas the response to ATP was enhanced (P <.05 for all). We conclude that electrogenic anion secretion occurs in human gallbladder mucosa under basal state and is stimulated by an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent pathway mediated by cystic fibrosis transmembrane conductance regulator (CFTR), and by exogenous ATP via a CFTR-independent pathway that is up-regulated in CF and involves P2Y2 purinoceptors and a calcium-dependent pathway.
Adenosine Triphosphate↗
Expression of delta F508 cystic fibrosis transmembrane conductance regulator protein and related chloride transport properties in the gallbladder epithelium from cystic fibrosis patients.
Cystic fibrosis transmembrane conductance regulator (CFTR), the cystic fibrosis (CF) gene product, functions as an adenosine 3', 5'-cyclic monophosphate (cAMP)-regulated chloride channel in the apical membrane of biliary epithelial cells, including gallbladder epithelial cells. It has been shown that triangle upF508, the most common CF mutation, impedes CFTR trafficking to the apical surface of epithelial cells. To elucidate the mechanisms of CF biliary disease, we examined structural features, CFTR expression, and chloride transport properties in gallbladder epithelial cells from nine triangle upF508 homozygous liver transplant recipients. Three CF patients had microgallbladders, characterized by severe histological abnormalities. Microgallbladder epithelial cells displayed aberrant immunolocalization of CFTR and of other normally apical proteins in the lateral domain of their plasma membrane and in their cytoplasm. This pattern was mimicked by chronic cholecystitis in non-CF patients. In the 6 remaining CF patients, CFTR was predominantly apical in the gallbladder epithelium, consistent with the detection of a fully glycosylated form by Western blot. In CF as compared with non-CF gallbladder epithelial cells in primary culture, chloride efflux was lower in response to cAMP and tended to be higher in response to exogenous adenosine 5'-triphosphate (ATP). The CF cells exhibited a residual cAMP-dependent chloride secretion that was inversely correlated with ATP-induced chloride secretion, and almost completely blunted in the cells derived from microgallbladders. Our results suggest that epithelial structural alterations aggravate triangle upF508 CFTR mislocalization in the gallbladder epithelium. The associated decrease in residual cAMP-dependent chloride secretion may contribute to biliary damage despite the up-regulation of alternative chloride transport pathways.
Adolescent↗
[Arterial air embolism as a complication of blunt thoracic trauma].
Systemic air embolism is a dramatic event frequently resulting in death. The clinical manifestations are polymorphic and unspecific. We report a case of a systemic air embolism in a patient with lung contusion. We wish to arouse a sensibility for this clinical picture, which seems to be underestimated in its frequency and importance, and discuss concepts of mechanical ventilation in patients with blunt thoracic trauma.
Adult↗
Lack of evidence for an immunosuppressive role for MUC1.
The in vitro anti-proliferative properties of various supernatants from MUC1-expressing cell lines and of purified preparations of MUC1 were evaluated. We have observed that supernatants from the MUC1-and MUC3-positive cell line T47D, but not from the MUC1- and MUC4-positive cell line MCF7, were able to inhibit proliferation of cells from various haematopoietic cell lines. Although the activity of T47D supernatants could be abrogated by immunodepletion of MUC1, immunopurified MUC1 from T47D was unable to inhibit cell proliferation. Significantly, supernatants from mouse 3T3 cells transfected with a secreted form of MUC1 or from BHK-21 cells infected with a recombinant vaccinia virus coding for the secreted form of MUC1, as well as preparations of purified MUC1 from bile or urine, were likewise unable to inhibit T cell proliferation. Surprisingly, a crude mixture of bile mucins had a suppressive effect on T cell growth. Our results suggest that other molecules, such as amino sugars or other mucins, which can associate with MUC1, are likely to be responsible for the observed anti-proliferative effects of T47D cells.
3T3 Cells↗
Combined abdominal wall paresis and incisional hernia after laparoscopic cholecystectomy.
A case of combined abdominal wall paresis and incisional hernia after laparoscopic cholecystectomy is reported. The paresis possibly occurred by a lesion of the N. intercostalis when extending the incision for stone extraction. Possibly the paresis was a predisposing factor for the development of an incisional hernia. The causes of abdominal wall paresis are explored with a review of the literature. In spite of minimal trauma to the anterior abdominal wall in laparoscopic procedures, the risk of iatrogenic lesions remains.
Abdominal Muscles↗
Involvement of mitogen-activated protein kinase homologues in the regulation of lipopolysaccharide-mediated induction of cyclo-oxygenase-2 but not nitric oxide synthase in RAW 264.7 macrophages.
In RAW 264.7 macrophages lipopolysaccharide (LPS) stimulated the activation of p42 and p44 MAP kinases and their upstream activator mitogen-activated protein (MAP) kinase kinase (MAPKK), and induced the 69-kDa isoform of cyclo-oxygenase-2 (COX-2) and the 130-kDa isoform of nitric oxide synthase (iNOS). PD 098059, a specific inhibitor of the activation of MAPKK, prevented LPS-mediated activation of MAPKK (IC50 = 3.0 +/- 0.1 microM, n = 3) and p42/44 MAP kinases and substantially reduced the induction of COX-2 by approximately 40%-70%, but was without effect upon the induction of iNOS. In parallel, LPS also stimulated the activation of p38 MAP kinase and the MAPKAP kinase-2, a downstream target of p38 MAP kinase. SB 203580, a specific inhibitor of p38 MAP kinase prevented the activation of p38 MAP kinase (IC50 = 3.3 +/- 1.4 microM, n = 3) and MAPKAP kinase-2 by LPS and reduced the induction of COX-2 by approximately 50-90%, with no significant effect upon iNOS expression. These studies indicate the involvement of both the classical p42/44 MAP kinases and p38 MAP kinase in the regulation of COX-2 but not iNOS induction following exposure to LPS.
Animals↗
Cognitive functioning in people with epilepsy plus severe learning disabilities: a systematic analysis of predictors of daytime arousal and attention.
In spite of the high prevalence of epilepsy and the importance of preserving cognitive function in people with learning disabilities, this population has received relatively little research attention. This study sets out systematically to investigate possible predictive factors of inter-ictal states of arousal and attention. The daytime function of 28 people with epilepsy and severe learning disabilities was assessed by performance on a two-choice reaction time vigilance task, behavioural analysis of time-sampled video recordings taken in naturalistic settings, and carer ratings on visual analogue scales. This methodology yielded eight discrete functional measures, from which two further index measures were derived after principal components analysis. A range of clinical and psychosocial assessments was completed and subjects had 36 hour ambulatory EEG and sleep EEG monitoring. Regression models identified significant predictors of cognitive function from a range of potential explanatory variables i.e. demographic, clinical, pharmacological, background EEG rhythms and sleep parameters. Results indicated that greater severity of learning disability, longer bedtime periods, poor sleep efficiency, frequent seizures and antiepileptic drug polytherapy were significant predictor variables. Explained variance (adjusted R2) was greater than 50% for six of 10 outcome variables (range up to 85%). Furthermore, significant regression equations (P < 0.05) were obtained for all but one variable. Thus, these results appear reasonably robust. Results support an interactional model of daytime arousal and attention in people with epilepsy plus severe learning disabilities. Inter-ictal cognitive function appears to be mediated by a combination of organic, circadian (sleep wake), clinical and pharmacological factors.
Adolescent↗
Spinal epidural abscess after tattooing.
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Abscess↗
Low-cholesterol and high-fat diets reduce atherosclerotic lesion development in ApoE-knockout mice.
We have investigated the effect of most common oils used in human nutrition on the development of atherosclerosis in apoE-knockout mice. Seven groups of animals, separated according to sex, were fed for 10 weeks either chow diet or the chow diet 10% (wt/wt) enriched with different oils (palm, coconut, 2 types of olive oil, and 2 types of sunflower oil) without addition of cholesterol. At the end of this period, plasma lipid parameters were measured and vascular lesions scored. None of the diets induced changes in plasma cholesterol concentrations, whereas plasma triglycerides were uniformly reduced in all diet groups. Some diets caused significant reductions in the size of atherosclerotic lesions in males and others in females; males responded most to sunflower oils and females to palm oil and one olive oil (II). The lesion reduction in males consuming sunflower oils was associated with the decrease of triglycerides in triglyceride-rich lipoproteins, whereas the decrease in females consuming olive oil II or palm oil was accompanied by an increase in plasma apoA-I. The increase in plasma apoA-I in the latter condition, is mainly due to overexpression of hepatic message elicited by a mechanism independent of apoE ligand. The data suggest that the different diets modulate lesion development in a gender specific manner and by different mechanisms and that the development of atherosclerosis, due to genetic deficiencies, may be modulated by nutritional maneuvers that may be implemented in human nutrition.
Animals↗
Color duplex sonography: diagnostic tool in the differentiation of inguinal hernias.
We investigated the accuracy of combined physical and color duplex sonographic examination in the preoperative distinction of direct inguinal hernias. After a learning period (with 15 male patients) 50 consecutive male patients who underwent surgery in our department for small inguinal hernias between July 1995 and April 1996 were examined. On color duplex examination the relationship between the hernial sac and the inferior epigastric artery was determined. Intraoperative results were then compared with the data obtained preoperatively. The sensitivity of our physical examination for direct inguinal hernia was 75% with a specificity and a positive predictive value of 100% and a negative predictive value of 80%. The identification of the IEA as well as the hernial sac was successful on every color duplex sonographic study. The sensitivity of color duplex sonography for direct inguinal hernias amounted to 90%, the specificity was 86%, the positive predictive value was 78%, and the negative predictive value was 89%. Both combined hernias found intraoperatively had not been detected either by physical examination or by color duplex examination. Correspondence of results obtained by physical examination and color duplex examination leads to high accuracy in the diagnosis of direct inguinal hernias.
Adult↗
Endothelin-1 is synthesized and inhibits cyclic adenosine monophosphate- dependent anion secretion by an autocrine/paracrine mechanism in gallbladder epithelial cells.
Ion and fluid transport across the biliary epithelium contributes to bile secretion. Since endothelin (ET)-1 affects ion transport activities and is released by human gallbladder- derived biliary epithelial cells in primary culture, we examined the expression of ET peptides and ET receptors and the influence of ET-1 on ion transport in this epithelium ex vivo. In freshly isolated gallbladder epithelial cells, preproET-1, -2, and -3 mRNAs were detected by reverse transcription PCR and ET-1 isopeptide was identified by chromatography. The cells also displayed ET receptor mRNAs and high-affinity binding sites for ET-1, mostly of the ETB type. Electrogenic anion secretion across intact gallbladder mucosa was stimulated by forskolin, secretin, and exogenous ATP, as assessed by short-circuit current (Isc) increases in Ussing-type chambers. ET-1 inhibited forskolin- and secretin-induced changes in Isc, without affecting baseline Isc or ATP-induced changes. Accordingly, ET-1 significantly reduced the accumulation of intracellular cAMP elicited by forskolin and secretin in the epithelial cells, and this effect was abolished by pertussis toxin. This is the first evidence that ET-1 is synthesized and inhibits, via a Gi protein-coupled receptor, cAMP-dependent anion secretion in human gallbladder epithelium, indicating a role in the control of bile secretion by an autocrine/paracrine mechanism.
Anions↗
Successful transplantation of porcine livers after warm ischemic insult in situ and cold preservation including postconditioning with gaseous oxygen.
BACKGROUND: In order to reduce the shortage of viable donor livers for organ transplantation, a method has been developed that allows even predamaged livers from nonheartbeating donors to be used as transplantable organs. METHODS: Porcine livers were harvested 45 min after cardiac arrest of the nonheparinized donor, preflushed with heparinized saline solution, and subsequently rinsed with University of Wisconsin solution, to which superoxide dismutase was added as an oxygen free radical scavenger. Thereafter, the livers were persufflated with gaseous oxygen via the venous vascular system while immersed in University of Wisconsin solution at 4 degrees C for 4 to 5 hr. RESULTS: After orthotopic transplantation, all of the livers conditioned with gaseous oxygen were able to support life-sustaining function during the whole observation period of 7 days post transplantation, while no survival of the recipients could be obtained without the described treatment. CONCLUSIONS: The present study establishes a new perspective for the use of ischemically altered livers from nonheartbeating donors for organ transplantation under clinical circumstances.
Animals↗
Lectin staining in the basal nucleus (Meynert) and the hypothalamic tuberomamillary nucleus of the developing human prosencephalon.
Previous studies have demonstrated that extracellular matrix glycoconjugates, shown by lectin-histochemistry with Vicia villosa agglutinin (VVA) and peanut agglutinin (PNA) as so-called perineuronal nets, play an important role in brain maturation. Concanavalin A (ConA) binding to neuronal surface glycoconjugates may be a marker of synaptic junctions. The present study was done to demonstrate the binding sites of these lectins in two functionally related nuclei of the prosencephalon, the basal nucleus (Meynert) and the hypothalamic tuberomamillary nucleus. Fetal brains of 16-36 weeks of gestation were examined by using VVA, PNA, and ConA to determine appearance and distribution patterns of specific lectin-binding sites on glycoconjugates during fetal brain development. The basal nucleus and the tuberomamillary nucleus showed a characteristic "cellular staining" that may have been due to cytoplasmatic labeling, surface labeling, or both. Lectin-staining occurred much earlier in the basal nucleus than in the tuberomamillary nucleus. Although all three lectins were bound to neurons of the basal nucleus, only ConA-positive neurons were observed in the tuberomamillary nucleus. In conclusion, lectin-labeled cells most probably represent projection neurons that are GABAergic (tuberomamillary nucleus) or cholinergic (basal nucleus). Labeling with the three lectins demonstrated nuclear-specific staining patterns that occur early in fetal development and gradually increase. Binding sites for lectins characterizing perineuronal nets (VVA, PNA) occurred only in the basal nucleus, whereas binding sites for ConA on neuronal-surface glycoconjugates, which seem to play a role in early synaptogenesis, were present in the basal and the tuberomamillary nucleus. The basal nucleus, however, expressed ConA binding sites distinctly earlier, probably indicating early arriving afferents.
Cell Nucleus↗
Endischemic oxygen persufflation to improve viability of marginally preserved donor livers.
The quality of cold-stored donor livers slowly declines beyond approximately 12 h, although these organs may still be used for clinical transplantation. The aim of the present study was to improve the energetic status and viability of long-term-preserved livers by short-term gaseous oxygen insufflation prior to implantation of the organ using a technique that has already been shown to promote aerobic energy metabolism during hypothermia. Livers from ten male Wistar rats were isolated, rinsed blood-free. Five livers (group 1) were stored for 48 h at 4 degrees C in UW preservation solution, and five livers (group 2) were isolated and stored in the same manner for 47 h, and were then, during the last 60 min of the preservation period, connected to a persufflation device and gaseous oxygen was introduced into the organ via the inferior caval vein, with the liver still immersed in cold UW solution. This technique of endischemic gaseous oxygenation resulted in a significant normalization of vascular resistance upon isolated reperfusion in vitro and a reduction in hepatic efflux of alanine aminotransferase as well as glutamate dehydrogenase, which led to improved recovery of the reperfused grafts of group 2 as evidenced by an elevated energy charge potential at the end of the reperfusion period. In conclusion, the technique described seemed effective in enhancing the preoperative viability of marginal donor grafts.
Animals↗