[Measuring the risk of infection after premature rupture of the membranes: consideration of complemenatary examinations and biological markers?].
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Amniocentesis↗
Biomedical subjects
P Hoffmann
Publications and source records attributed to P Hoffmann.
Epileptiform activity induced by 4-aminopyridine in entorhinal cortex hippocampal slices of rats with a genetically determined absence epilepsy (GAERS).
Patients with absence epilepsy frequently develop convulsions later in life. We were therefore interested whether tissue from rats with a genetic absence epilepsy is more prone to seizure generation than normal animals. We compared the epileptiform activities induced by 4-aminopyridine (4-AP) induced in hippocampal-entorhinal cortex slices from genetic absence epilepsy rats of Strasbourg (GAERS, age 6 months) in which absence seizures have been present for about 4 months and from control non epileptic rats (NE). 4-AP induced short recurrent discharges in area CA1 of rat hippocampus, seizure-like events and interictal discharges in the entorhinal cortex. The various epileptiform discharges did not differ between the two strains in amplitude, duration and frequency. However, the latency for induction of different epileptiform activities by 50 microM 4-AP was significantly shorter in GAERS (about 16 min) than in NE rats (about 25 min). We also analysed differences in evoked field potentials (fp) in hippocampal area CA1 before, during and after application of 4-AP. Before application of 4-AP, responses to stimulation of Schaffer collateral were smaller in GAERS than in NE rats. Paired pulse potentiation was significantly larger in GAERS than in NE rats. 4-AP in the bath augmented the size of the evoked field potentials and this increase was larger in GAERS than in NE rats. Our findings show a greater excitability of hippocampal area CA1 in GAERS rats and a greater ability to develop 4-AP-induced epileptiform activity in combined hippocampal-enthorhinal cortex slices in GAERS than in NE rats.
4-Aminopyridine↗
Bioavailability of hydrocarbons during microbial remediation of a sandy soil.
The microbial degradation of hydrocarbons was studied in an artificially contaminated sandy soil, using a pilot-scale percolator system. After a short lag period, an intensive degradation occurred, which diminished in time and completely stopped in the end, despite large residual contaminations (residues of 56% diesel fuel, 20% n-hexadecane and 3.5% phenanthrene at the initial loadings of each 3000 mg/kg). The remaining pollutant content was influenced by the kind of hydrocarbon but was nearly independent of its initial loading. According to a model-aided analysis of the carbon dioxide production during remediation, the observed stagnation of degradation was caused by a limited bioavailability of the pollutants. The degradation in the soil-free aqueous phase was more extensive than in the soil, which suggests that the limited bioavailability in the soil can be attributed mainly to matrix-dependent rather than substrate-dependent influences. Generally, fine particles and organic matter are mainly responsible for the adsorption of pollutants to the soil matrix. Our sandy soil also bound hydrocarbons adsorptively although it contained neither silty material nor significant amounts of organic matter. As shown by Brunauer Emmett Teller (BET) analysis, the soil particles were covered by micropores, which enlarged the soil surface by a factor of 120 in comparison with the macroscopic surface area. The microporosity is the reason for the hydrocarbons being more strongly adsorbed to the sandy soil than expected.
Biodegradation, Environmental↗
The antithrombotic efficacy of the GP IIb/IIIa antagonist SR121787 is potentiated by antithrombin-dependent factor Xa inhibition without an increase in the bleeding risk in the rabbit.
Current antithrombotic therapy in acute coronary symptoms is only partially effective and exhibits bleeding complications. These experiments were designed to address the antithrombotic and hemorrhagic interactions of the novel glycoprotein (GP) IIb/IIIa antagonist SR121787 in combination with the indirect inhibitor of factor Xa, SR90107/ORG31540. Thrombogenesis was initiated by electrolytic injury of the intimal surface of the carotid artery, and thrombus formation was assessed by recording carotid blood flow and by measuring thrombus weight 45 min after electrical stimulation. SR121787 was an efficacious antithrombotic agent in this model (ED50 = 16.3+/-0.3 mg/kg, p.o.), whereas heparin (4.5 mg/kg, i.v.) and SR90107/ORG31540 [1 mg/kg (850 aXa anti-units/kg), i.v.] were only marginally effective (17 and 27% inhibition of carotid blood flow reduction, respectively). Coadministrations of heparin (4.5 mg/kg, i.v.) or SR90107/ORG31540 (0.5 mg/kg, i.v.) were found to potentiate the antithrombotic efficacy of threshold doses of SR121787 (5 or 10 mg/kg, p.o.). The enhancement of the antithrombotic efficacy of SR121787 by SR90107/ORG31540 was--contrary to the association of SR121787 with heparin--not accompanied by an increased blood loss from the incised rabbit ear. Coadministrations of heparin or SR90107/ORG31540 did not influence the ex vivo antiaggregatory activity of SR121787. SR121787 coadministration did not alter the systemic anticoagulant activities in heparin or SR90107/ORG31540-treated animals. These data suggest the potential for optimized antithrombotic treatment in acute coronary syndromes when a GP IIb/IIIa antagonist (SR121787) is combined with an antithrombin-dependent factor Xa inhibitor (SR90107/ORG31540).
Animals↗
Interspecies comparison of the antiplatelet, antithrombotic, and hemorrhagic effects of SR 121566A, a novel nonpeptide GP IIb/IIIa antagonist.
We report the results from an interspecies comparison of the antiplatelet, antithrombotic, and hemorrhagic actions of SR 121566A, a novel nonpeptide antiplatelet agent with high affinity and specificity for the GP IIb/IIIa complex. SR 121566A exhibited in vitro antiplatelet activity against adenosine diphosphate (ADP)-induced aggregation with a rank order of potency [humans = baboons = dogs] > marmosets > guinea pigs > rabbits. These in vitro findings were predictive for the ex vivo antiplatelet potency after i.v. administration of SR 121566A to dogs, guinea pigs, and rabbits [median effective dose (ED50) values, 0.02, 0.05, and 0.15 mg/kg]. The antiplatelet actions of SR 121566A translated into an acute antithrombotic effect in an arteriovenous shunt model after i.v. administration in dogs, guinea pigs, rabbits, and marmosets (ED50, 0.08, 0.10, 0.50, and 0.007 mg/kg). Hemorrhagic effects of SR 121566A were observed in guinea pigs and rabbits at doses that represented 2-3 times the antithrombotic ED50, whereas in marmosets, no bleeding was observed at the antithrombotic ED90. These results demonstrate that SR 121566A exhibits favorable actions in terms of antithrombotic potency and hemostatic safety in different animal species, suggesting that, in humans, SR 121566A will be a good candidate as an antithrombotic compound.
Adenosine Diphosphate↗
Epidermal growth factor increases basal mucosal blood flow in the rat colon, a prostaglandin dependent effect.
OBJECTIVE/BACKGROUND: Non-mitogenic biological activity such as modulation of mucosal blood flow is suspected to convey the protective effects of epidermal growth factor (EGF) in vivo. The aims of our present study were to determine the effects of EGF on colonic mucosal blood flow and injury induced hyperaemia in rats. DESIGN/METHODS: Rats were pretreated with i.p. injections of vehicle, EGF, or indomethacin and EGF prior to mucosal injury. Basal mucosal blood flow and injury induced hyperaemia at the border of the damaged mucosa was determined by using reflectance spectrophotometry. RESULTS: EGF significantly increased basal mucosal blood flow but did not further enhance injury induced hyperaemia. The EGF induced increase in basal mucosal blood flow was completely abolished by indomethacin pretreatment. CONCLUSIONS: EGF induces an increase of basal mucosal blood flow through induction of prostaglandin synthesis. We hypothesize that the increase in mucosal blood flow contributes to the ability of EGF to protect the colonic mucosa against injury.
Animals↗
Novel donors of nitric oxide derived of S-nitrosocysteine possessing antioxidant activities.
Novel S-nitrosothiols possessing a phenolic function were investigated as nitric oxide (NO) donors. A study of NO release from these derivatives was carried out by electron spin resonance (ESR). All compounds gave rise to a characteristic three-line ESR signal in the presence of the complex [Fe(II)(MGD)2], revealing the formation of the complex [Fe(II)(MGD)2(NO)]. Furthermore, tests based on cytochrome c reduction were performed in order to study the ability of each phenolic disulfide, the final organic decomposition product of S-nitrosothiols, to trap superoxide radical anion (O2-). This study revealed a high reactivity of 1b and 3b towards O2-. For these two compounds, the respective inhibitory concentration (IC) 50 values were 92 microM and 43 microM.
Antioxidants↗
Uptake of NO-releasing drugs by the P2 nucleoside transporter in trypanosomes.
Nitric oxide (NO.) has been identified as a principal regulatory molecule of the immune system and the major cytotoxic mediator of activated immune cells. NO. can also react rapidly with a variety of biological species, particularly with the superoxide radical anion O2.- at almost diffusion-limited rates to form peroxynitrite anion (ONOO-). ONOO- and its proton-catalyzed decomposition products are capable of oxidizing a great diversity of biomolecules and can act as a source of toxic hydroxyl radicals. As a consequence, a strategy for the development of molecules with potential trypanocidal activities could be developed to increase the concentration of nitric oxide in the parasites through NO.-releasing compounds. In this way, the rate of formation of peroxynitrite from NO. and O2.- would be faster than the rate of dismutation of superoxide radicals by superoxide dismutases which constitute the primary antioxidant enzymatic defense system in trypanosomes. The adenosine transport systems of parasitic protozoa, which are also in certain cases implicated in the selective uptake of active drugs such as melarsoprol or pentamidine, could be exploited to specifically target these NO.-releasing compounds inside the parasites. In this work, we present the synthesis, characterization and biological evaluation of a series of molecules that contain both a group which would specifically target these drugs inside the parasites via the purine transporter, and an NO.-donor group that would exert a specific pharmacological effect by increasing NO level, and thus the peroxynitrite concentration inside the parasite.
Adenosine↗
Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group.
The chimeric anti-TNF antibody Remicade (Infliximab) has recently been approved for human use by the FDA and is now available on the market. Since there is considerable interest in this kind of treatment among patients with Crohn's disease, an international working group has summarized the presently available information about efficacy, side effects and possible problems of this treatment. Studies show that Remicade is effective in the treatment of active Crohn's disease, maintaining remission and fistulae. The working group does not see Infliximab as a first-line treatment for Crohn's disease. It may be used in active phase recurrent disease, chronic active disease and fistulae if standard treatment was not successful. For the surveillance special attention has to be given to the unknown malignancy rate of Infliximab. Infusion should be performed in an institution, routinely performing intravenous infusions and a two-hour surveillance of the patients should be guaranteed to recognize anaphylactic reactions or acute side effects. There is presently no information indication that the combination with immunosuppressants might increase risks or side effects of this treatment. Due to the limited information available the working group would prefer to use Remicade in studies only and recommends central collection and documentation of all data on efficacy and side effects for the next year.
Antibodies, Monoclonal↗
[Families of patients in intensive care: nurses help them throughout the crisis].
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Child, Hospitalized↗
[Interscalene plexus block for mobilizing chronic shoulder stiffness].
INTRODUCTION: After mobilisation of a frozen shoulder, patients should work with a physiotherapist one to two times a day. In the remaining time patients must exercise on their own: otherwise, the shoulder is likely to become less mobile. Exercise is only possible in the absence of pain. Therefore, adequate analgesic therapy for four to five days after the first mobilisation is of great importance. We used interscalene blockade of the brachial plexus to achieve mobilisation in patients suffering from a painful frozen shoulder. We investigated the efficacy of this technique by registering the use of additional analgesics and documenting the patient's assessment. The observation time was 18 months. METHODS: Thirty-seven patients were treated with a plexus block using a catheter inserted at the affected side. Catheter location was verified with electric nerve stimulation. In all patients a bolus of 20 ml bupivacaine 0.375% was given for initial mobilisation, followed by 10 ml bupivacaine 0.25% every 6 hours. RESULTS: In 34 of 37 (92%) patients, the shoulder could be mobilised without general anaesthesia. Thirty-three of 37 (89%) patients did not need any additional analgesics during the following mobilizations. The mean duration of catheter treatment was 4 days; no infections occurred. The following side effects were observed at the first mobilisation: Horner's syndrome in 20 patients (54%), paresis of the recurrent nerve in 9 patients (24%) and paresis of the phrenic nerve in 6 patients (16%). During subsequent treatment, Horner's syndrome was observed in 15 patients (41%) and a paresis of the recurrent nerve in 8 patients (22%). In an interview after the end of the treatment period all patients stated that they would use this method again if necessary. CONCLUSIONS: With the use of this regional anaesthesia technique it was possible to provide comfortable pain therapy during the mobilisation period. In order to achieve sufficient analgesia with only a mild motor blockade of the motoneurons, the exact location of the catheter tip is important. The latter can be verified by electrical stimulation.
Adult↗
Epileptiform activity and changes in field potential responses induced by low [Mg2+]0 in a genetic rat model of absence epilepsy.
The genetic absence epilepsy rats of Strasbourg (GAERS) display alterations in cortical synaptic transmission possibly facilitating the generation of ictaform activity and the late development into convulsive epilepsy. We studied low Mg2+-induced epileptiform activities and their long term effects on field potentials (fp) evoked by paired pulse stimulation in hippocampal area CA1 (CA1), medial entorhinal cortex (EC) and frontal cortex (FC) in in-vitro-slice preparations from GAERS and control (NE) adult rats (6 months). Omitting Mg2+-ions from artificial cerebrospinal fluid (ACSF) caused recurrent short discharges (in CA1) and seizure-like events (in EC) in both GAERS and NE rats. Latency to onset of activity as well as discharge pattern, frequency and amplitude of such events did not differ between the two strains, neither in CA1 nor in EC. In the FC, however, epileptiform events occurred in NE rats, but not in GAERS. Field potentials in normal ACSF were similar in both strains in CA1 and FC, while they were smaller in the EC of GAERS. Low [Mg2+]0 caused long-term changes of fp only in area CA1 where the population spikes were depressed in GAERS and increased in NE rats. We concluded that susceptibility to low [Mg2+]0-induced epileptic activity in EC and hippocampal area CA1 is not higher in GAERS than in NE adult rats. However, some properties like synaptic coupling in EC and long-term changes in synaptic efficacy induced by epileptiform activity in CA1 differ from that in NE rats. Whether the particularities in GAERS may be related to kindling by absence epileptic activities will be studied in further experiments.
Animals↗
Biochemical and pharmacological properties of SANORG 34006, a potent and long-acting synthetic pentasaccharide.
SANORG 34006 is a new sulfated pentasaccharide obtained by chemical synthesis. It is an analog of the "synthetic pentasaccharide" (SR 90107/ ORG 31540) which represents the antithrombin (AT) binding site of heparin. SANORG 34006 showed a higher affinity to human AT than SR 90107/ORG 31540 (kd = 1.4 +/- 0.3 v 48 +/- 11 nmol/L), and it is a potent and selective catalyst of the inhibitory effect of AT on factor Xa (1,240 +/- 15 anti-factor Xa U/mg v 850 +/- 27 anti-factor Xa U/mg for SR 90107/ORG 31540). In vitro, SANORG 34006 inhibited thrombin generation occurring via both the extrinsic and intrinsic pathway. After intravenous (IV) or subcutaneous (SC) administration to rabbits, SANORG 34006 displayed a long-lasting anti-factor Xa activity and inhibition of thrombin generation (TG) ex vivo. SANORG 34006 was slowly eliminated after IV or SC administration to rats, rabbits, and baboons, showed exceptionally long half-lives (between 9.2 hours in rats and 61.9 hours in baboons), and revealed an SC bioavailability near 100%. SANORG 34006 displayed antithrombotic activity by virtue of its potentiation of the anti-factor Xa activity of AT. It strongly inhibited thrombus formation in experimental models of thromboplastin/stasis-induced venous thrombosis in rats (IV) and rabbits (SC) (ED50 values = 40.0 +/- 3.4 and 105.0 +/- 9.4 nmol/kg, respectively). The duration of its antithrombotic effects closely paralleled the ex vivo anti-factor Xa activity. SANORG 34006 enhanced rt-PA-induced thrombolysis and inhibited accretion of 125I-fibrinogen onto a preformed thrombus in the rabbit jugular vein suggesting that concomitant use of SANORG 34006 during rt-PA therapy might be helpful in facilitating thrombolysis and preventing fibrin accretion onto the thrombus under lysis. Contrary to standard heparin, SANORG 34006 did not enhance bleeding in a rabbit ear incision model at a dose that equals 10 times the antithrombotic ED50 in this species and, therefore, exhibited a favorable therapeutic index. We suggest that SANORG 34006 is a promising compound in the treatment and prevention of various thrombotic diseases.
Animals↗
Partial ureteral duplication in an inverted Y with epididymal ureteric ectopia and intrasinusal ureteral junction.
Partial ureteral duplication in an inverted Y is evidenced by the presence of a ureter duplicated at a variable level before reaching the bladder, in either an orthotopic or an ectopic position. A case of ureteral duplication at the level of the renal hilum with opening of a ureter at the level of the epididymis is reported. The description of this original case is compared with the data in the literature. The stages of organogenesis of the superior excretory pathway leading to ureteral ectopia and ureteral anomalies of number are reviewed.
Abnormalities, Multiple↗
A fetal sheep liver extract reverses age-related increments in spontaneous and induced cytokine production by indirect environmental effects.
BALB/c, DBA/2 and C57BL/6 mice of different ages (ranging from 8 to 110 weeks of age) were used as spleen cell donors to assay cytokine production from ConA activated spleen and Peyer's Patch (PP) lymphocytes. As reported in an earlier publication, there was an age-related decline in IL-2 production in all strains, with a general increase in IL-4 and IL-10 production with age, this being particularly marked for PP cell preparations. Similar conclusions were reached from independent analysis of CD44hi and CD44lo cell populations in these groups (memory vs. naive cells, respectively). Interestingly, IL-6 production was dramatically increased (some 4-5-fold in the different strains) and significantly increased levels of IL-6 were detected in the serum of aged mice. A previously described sheep fetal liver extract was able to reverse, to varying degrees, these cytokine changes associated with aging. Interestingly, when cells from aged mice were adoptively transferred to lethally irradiated young (8 week) recipients, the cytokine production phenotype of cells harvested from recipient mice 3 weeks later was that of the aged donor, unless recipients were treated continually with extract. Treatment of the donor alone produced minimal changes in cytokine production 3 weeks following adoptive transfer. The effect of extract was reversed in treated aged mice by concomitant daily intravenous infusion of the competitive inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine (NMMA)), which also decreased the increased serum nitrate levels in mice treated with extract. Our data suggest an important role for reactive nitrogen products, themselves induced by fetal liver extract, in age-associated changes in cytokine production.
Adoptive Transfer↗
Increase in nitric oxide formation after chronic voluntary exercise in spontaneously hypertensive rats.
The effect of chronic voluntary exercise on the plasma level of nitrate, a major stable metabolite of nitric oxide (NO) was studied in spontaneously hypertensive rats (SHR). Exercise consisted of spontaneous running in wheels for 3-35 days. Blood samples were collected after 3, 7, 14, 21 and 35 days of exercise and all samples were drawn after the running wheel had been locked during the preceding 12 h. The plasma nitrate level was significantly (P < 0.05) elevated in SHR after 35 days of exercise. Surprisingly after 7 days of exercise a significant (P < 0.001) decrease in the nitrate level in plasma was noted. Further research is needed to elucidate this biphasic change in nitrate seen in this study. The elevated level of plasma nitrate seen after 35 days of voluntary exercise was still present up to 36 h after termination of exercise. We conclude that exercise training in SHR elicits an enhanced formation of NO.
Animals↗
Balloon catheter dilatation in the treatment of ureteral and ureteroenteric stricture.
Balloon catheter dilatation is a low-cost alternative to open surgery in patients with ureteral strictures, leading to low morbidity and short hospitalization. The goal of this study was to evaluate the results of this technique in patients with inflammatory ureteral strictures or ureteroenteric strictures after radical cystectomy. Twenty-five ureteral strictures in 20 (15 male, 5 female) patients were consecutively treated by high-pressure balloon dilatation: 14 cases of ureteroenteric stricture (9 after ileal cutaneous diversion, and 5 after orthotopic enterocystoplasty) and 11 of ureteral stricture from various inflammatory causes (tuberculosis, iatrogenic injury, radiation therapy, parasitosis). Dilatation was performed by an antegrade (ureteroenteric strictures) or retrograde (inflammatory strictures) approach using a balloon insufflated up to 10 to 20 atm for 5 to 15 minutes. The ureter was stented for a mean time of 2.1 months (range 1-5 months). Results were evaluated clinically and radiologically (intravenous urogram or CT scan). Immediate success was assessed by intraoperative radiologic monitoring. Long-term success was defined as the absence of recurrence of the stenosis after 6 months. Nineteen procedures were successful among the 23 evaluable cases. With a mean follow-up of 16 months (range 6-39 months), the long-term success rate was 52%: 40% in ureteral strictures and 61% in ureteroenteric strictures. Five strictures secondary to cutaneous diversion and six caused by radiation therapy recurred after dilatation. After cutaneous diversion, the failure occurred mostly at the anastomosis and involved the crossed-over ureter. This study shows that high-pressure balloon dilatation of ureteral strictures has a high early success rate and a long-term success rate of 52%. It can therefore be considered as an alternative to open surgery.
Adult↗
Morphological changes during early trans-tibial prosthetic fitting.
Morphological changes in the amputation stump may have serious implications regarding the suspension and fit of the prosthetic socket. In an earlier study (Lilja and Oberg, 1997) the authors have shown that the volume of the trans-tibial amputation stump decreases according to a negative power function after amputation, and that the stump volume does not stabilise until four months after the operation. In the present study, Magnetic Resonance Imaging (MRI) technique was used to examine morphological changes in the amputation stump after trans-tibial amputation in a small number of cases. The authors expected to find a decrease in the cross-sectional area of the stump and of the separate muscles similar to the findings in earlier studies. However, two different patterns were found. The cross-sectional area of the entire stump as well as that of the medial muscle group changed according to the authors' hypothesis, i.e. an initial fast decrease, followed by a more moderate decrease of the area. In the lateral muscle group another pattern was found. After an initial rapid decrease the area increased, sometimes to a magnitude larger than the initial value. After the amputation the lateral muscle group may acquire a new function, contributing to the suspension of the socket. Despite the limited number of patients, this study presents findings which may be important in the clinical fitting of trans-tibial prostheses.
Aged↗