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E Martin

Publications and source records attributed to E Martin.

At least 91 records · Page 5Linked to original sources
PubMed2001

Delayed effects of tamoxifen in hepatocarcinogenesis-resistant Fischer 344 rats as compared with susceptible strains.

The anti-oestrogenic drug tamoxifen has been under investigation as a breast cancer chemopreventive agent for at least a decade. However, its use for this purpose is still debatable since it is able to induce liver tumours in rats via a mechanism involving metabolic activation to a DNA adduct-forming electrophilic intermediate. The metabolic activation and adduct-forming properties of tamoxifen are now well characterized but less is known about its ability to induce hepatic cell proliferation, which is also essential for the carcinogenic process. The effects of tamoxifen on liver weight and cell proliferation were compared in female Fischer 344 (F344), Wistar and Lewis rats given the drug in the diet for up to 26 weeks. The onset and duration of hepatic cell proliferation varied between the strains of rat. In Wistar and Lewis but not F344 rats there was a marked increase in hepatocellular proliferation during the first 4 weeks of tamoxifen administration. In the Wistar strain this was associated with an increase in DNA adduct levels; no such increase was observed in the F344 strain. The onset of the proliferative response was delayed until the 13 week time point in the F344 strain. By the 13 and 26 week time points, cell proliferation in tamoxifen-treated Wistar and Lewis rat liver had returned to normal, but the amount of apoptotic activity in these livers was elevated. This suggests that excess cells generated during the proliferative phase of tamoxifen treatment were being eliminated by apoptosis. In the F344 strain, however, increased proliferative activity was associated with relatively low apoptotic activity at the 26 week time point, suggesting that the delayed proliferative response had yet to be balanced by apoptotic deletion. This is consistent with the fact that tamoxifen-induced hepatocellular tumours develop very late, towards the end of the lifespan, in this strain. The cell proliferative activity of tamoxifen in the Wistar rat liver was compared with that of a non-mutagenic analogue, toremifene. Tamoxifen induced increased cell cycle activity in the livers of rats following gavage dosing at all sampling times (1-12 weeks), whereas toremifene had no effect on the incidence of cycling in hepatic cells, demonstrating that the hepatic cell proliferation is not a general response to anti-oestrogen treatment. These observations suggest that the rate of promotion of liver tumours by tamoxifen is a function of the rate, time of onset and duration of increased cell replication. The susceptibility of rat strains to the hepatocarcinogenic effects of tamoxifen appears to depend upon the balance between initiation via DNA adduct formation, promotion via increased cell proliferation and cell deletion via apoptosis. Our findings suggest that an early proliferative response to tamoxifen is important in this process.

Animals↗
PubMed2001

Proton magnetic resonance spectroscopy of the brain of a neonate with nonketotic hyperglycinemia: in vivo-in vitro (ex vivo) correlation.

Nonketotic hyperglycinemia (NKH) is an inborn error of amino acid metabolism caused by a defect in the glycine cleavage multienzyme complex resulting in high concentrations of glycine within the brain and spinal cord. Quantitative magnetic resonance spectroscopy ((1)H-MRS) allows measurement of absolute glycine concentrations within different parts of the brain in vivo. In addition, (1)H-MRS may be useful in monitoring treatment of NKH and to differentiate this disease from other disorders of glycine metabolism.

Brain↗
PubMed2001

N-acetylcysteine attenuates the increase in alpha-glutathione S-transferase and circulating ICAM-1 and VCAM-1 after reperfusion in humans undergoing liver transplantation.

BACKGROUND: Oxidative stress and leukocyte-endothelial interactions contribute significantly to the reperfusion injury of the transplanted liver. Therefore, we investigated the effect of N-acetylcysteine (NAC) on reperfusion injury and circulating adhesion molecules during human liver transplantation. METHODS: In a prospective study, 10 orthotopic liver transplantation patients were treated with high-dose NAC and 10 patients were treated with 5% glucose (placebo group) immediately before and during reperfusion of the donor liver. Parameters of hepatocellular injury, cellular oxygenation, plasma cytokines, and circulating adhesion molecules were determined at various time points during the liver transplantation. RESULTS: NAC had no significant effect on the arterial lactate/pyruvate or hydroxybutyrate/acetoacetate ratio during the liver transplantation. At baseline, liver transplantation patients exhibited elevated levels of cytokines and circulating adhesion molecules compared with healthy volunteers (n=7). While no significant effect of NAC on circulating L- and P-selectin was observed, it significantly inhibited the increase in circulating ICAM-1 and VCAM-1 24 hr after reperfusion. There were no significant differences in maximal postoperative values of serum aspartate transaminase (peak AST) or alanine transaminase (peak ALT) between both groups. However, NAC significantly reduced the rise in alpha-glutathione S-transferase after reperfusion of the donor liver. CONCLUSIONS: NAC attenuated the increase in alpha-glutathione S-transferase and circulating ICAM-1 and VCAM-1 after reperfusion of the donor liver, indicating possible cytoprotective effects of NAC.

Acetylcysteine↗
PubMed2001

Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and outcome after cardiac arrest in humans.

BACKGROUND: The results of early conventional tests do not correlate with cerebral outcome after cardiac arrest. We investigated the serum levels of astroglial protein S-100 as an early marker of brain damage and outcome after cardiac arrest. METHODS AND RESULTS: In 66 patients undergoing cardiopulmonary resuscitation after nontraumatic cardiac arrest, blood samples for the evaluation of S-100 were drawn immediately after and 15, 30, 45, and 60 minutes; 2, 8, 24, 48, and 72 hours; and 7 days after initiation of cardiopulmonary resuscitation. Moreover, the serum levels of neuron-specific enolase were determined between 2 hours and 7 days. If patients survived for >48 hours, brain damage was assessed by a combination of neurological, cranial CT, and electrophysiological examinations. Overall, 343 blood samples were taken for the determination of S-100. Maximum S-100 levels within 2 hours after cardiac arrest were significantly higher in patients with documented brain damage (survivors and nonsurvivors, 3.70+/-0.77 microg/L) than in patients without brain damage (0.90+/-0.29 microg/L). Significant differences between these 2 groups were observed from 30 minutes until 7 days after cardiac arrest. In addition, the positive predictive value of the S-100 test at 24 hours for fatal outcome within 14 days was 87%, and the negative predictive value was 100% (P<0.001). With regard to neuron-specific enolase, significant differences between patients with documented brain damage and those with no brain damage were found at 24, 48, and 72 hours and 7 days. CONCLUSIONS: Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and short-term outcome after cardiac arrest in humans.

Adult↗
PubMed2001

Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial.

BACKGROUND: During cardiopulmonary resuscitation (CPR), thrombolysis can help to stabilise patients with pulmonary embolism and myocardial infarction. Moreover, thrombolysis during CPR has beneficial effects on cerebral reperfusion after cardiac arrest. We investigated this new therapeutic approach in patients in whom conventional CPR had been unsuccessful. METHODS: We assessed, in a prospective study, patients undergoing CPR after out-of-hospital cardiac arrest for cardiological reasons in whom return of spontaneous circulation was not achieved within 15 min. According to the Ustein criteria, our control group consisted of patients who were assessed during 1 year. After this year patients were treated with a bolus of 5000 U of heparin and 50mg, over 2 min, of tissue-type plasminogen activator (rt-PA treated group). This intervention was repeated if return of spontaneous circulation was not achieved within the following 30 min. For controls only CPR was given. FINDINGS: Overall, 90 patients were included; heparin and rt-PA were given to 40 patients. There were no bleeding complications related to the CPR procedures. Of the rt-PA group, 68% (27) had return of spontaneous circulation and 58% (23) were admitted to a cardiac intensive care unit, compared with 44% (22; p=0.026) and 30% (15; p=0.009) of the controls, respectively. At 24 h after cardiac arrest a larger proportion of the rt-PA group than of the controls was alive (35% [14] vs 22% [11], p=0.171), and 15% (six) of rt-PA-treated patients and 8% (four) of controls could be discharged from hospital. INTERPRETATION: After initially unsuccessful out-of-hospital CPR, thrombolytic therapy combined with heparin is safe and might improve patient outcome. On the basis of our data a randomised controlled trial might be regarded as ethical.

Aged↗
PubMed2001

Severe arterial occlusive disorder and brachysyndactyly in a boy: a further case of Grange syndrome?

We report on a 15-year-old boy with stenosis and occlusion of multiple cranial, renal, and celiac arteries, aneurysm of the basilar artery, bilateral cutaneous syndactyly between fingers IV-V, partial cutaneous syndactyly between fingers III-IV on the right hand, brachydactyly, and borderline mental retardation. The clinical course was characterized by recurrent abdominal pain, gastritis, and high blood pressure. The pattern of the clinical and radiological findings is different from fibromuscular dysplasia (FMD) and Moyamoya disease, and highly suggestive of a syndrome described by Grange in four siblings (MIM#602531) Grange et al. [1998: Am J Med Genet 75: 469-480].

Abnormalities, Multiple↗
PubMed2001

Two domains of the human bZIP transcription factor TCF11 are necessary for transactivation.

TCF11 is a bZIP transcription factor of the CNC subfamily. It has been implicated in the regulation of the antioxidant response and is vital during embryonic development, but its precise biological functions have not yet been fully worked out. Structural characterization of the gene and several of its products indicates that complex regulatory mechanisms are employed. To investigate how altering the structure of the gene products might influence their activity we have mapped functional domains within the protein. We show that two separate domains are required for transactivation by full-length TCF11: an N-terminal acidic domain and a serine-rich stretch adjacent to the CNC-bZIP domains. A naturally occurring shorter isoform (identical to LCR-F1) produced by internal initiation of translation is unable to transactivate in our assay. However, the shorter form could interfere with the transactivating ability of the longer form, which indicates a control mechanism for keeping the activity of TCF11 at a desired level. We show that TCF11 and the closely related CNC-bZIP factor p45 NF-E2 show different cell type-specific activation patterns with full-length TCF11 being active in COS-1 cells but silent in erythroid cells (K562), whereas p45 NF-E2 is active in K562 cells and silent in COS-1 cells. Domain swapping experiments show that cell type-specific activity is not fully determined by dimerization/DNA binding domains or transactivation domains alone. The resulting profile of activity is most likely achieved by interaction of the domains and their cell-specific environment.

Humans↗
PubMed2001

DNA encoding a single mycobacterial antigen protects against leprosy infection.

The continuing incidence of leprosy infection around the world and the inability of Mycobacterium bovis bacille Calmette-Guérin (BCG) to protect certain populations clearly indicates that an improved vaccine against leprosy is needed. The immuno dominant 35 kDa protein, shared by Mycobacterium leprae and Mycobacterium avium, but not Mycobacterium tuberculosis or BCG, is recognised by >90% of leprosy patients, making it an ideal candidate antigen for a subunit vaccine. Immunization of outbred Swiss Albino mice with a DNA-35 vaccine stimulated specific T cell activation and IFN-gamma production. DNA-35 immunization induced significant levels of protection against M. leprae footpad infection, comparable to that produced by BCG. Therefore, DNA immunization with the 35 kDa antigen is effective against M. leprae infection and genetic immunization with a combination of antigens holds the potential for an improved vaccine against leprosy.

Animals↗
PubMed2001

Brain blood flow changes in depressed patients treated with interpersonal psychotherapy or venlafaxine hydrochloride: preliminary findings.

BACKGROUND: Functional brain imaging studies in major depression have suggested abnormalities of areas, including the frontal cortex, cingulate gyrus, basal ganglia, and temporal cortex. We hypothesized that venlafaxine hydrochloride and interpersonal psychotherapy (IPT) might each alter brain blood flow in some or all of these areas on sequential single photon emission computed tomography (SPECT) scans. METHODS: Twenty-eight men and women aged 30 to 53 years with a DSM-IV major depressive episode, a 17-item Hamilton Rating Scale for Depression (HAM-D) rating of 18 or higher, and antidepressant-naive for at least 6 months were studied. After baseline (99m)technetium-hexa-methyl-propylene-amine-oxime scan, 1-T magnetic resonance imaging, and psychometric ratings, patients were assigned to different treatments. Thirteen patients had 1-hour weekly sessions of IPT from the same supervised therapist (E.M.). Fifteen patients took 37.5 mg twice-daily of venlafaxine hydrochloride. Single-photon emission computed tomography scans and ratings were repeated at 6 weeks. RESULTS: Both treatment groups improved substantially, more so with venlafaxine (mean [SD] HAM-D scores at pretreatment: IPT, 22.7 [2.7], and venlafaxine, 22.4 [3.1]; and posttreatment: IPT, 16.2 [7.1], and venlafaxine, 10.9 [8.6]). No patients had structural brain abnormalities. On analysis with statistical parametric mapping 96, the venlafaxine group showed right posterior temporal and right basal ganglia activation (P =.01), while the IPT group had limbic right posterior cingulate and right basal ganglia activation (P =.01). CONCLUSIONS: This preliminary investigation has shown limbic blood flow increase with IPT yet not venlafaxine, while both treatments demonstrated increased basal ganglia blood flow. This was, however, a short trial with a small sample, no control group, and different symptom reduction in the 2 groups.

Adult↗
PubMed2001

[Cisatracurium in coronary bypass operations--a comparison with pancuronium. Hemodynamic and neuromuscular effects in patients under chronic beta blocker treatment].

OBJECTIVE: The aim of the study was to compare haemodynamic and neuromuscular effects of cisatracurium and pancuronium in patients undergoing coronary artery bypass grafting (ASA III, good or moderately impaired LV function) who were chronically medicated with beta-adrenergic blocking agents. METHODS: 60 Patients were randomly assigned in a double-blind fashion to receive sufentanil/midazolam/etomidate and either pancuronium (2xED95, group P) or cisatracurium (2xED95, group C2 and 4xED95, group C4). Haemodynamic variables were measured using arterial and pulmonary arterial catheters, neuromuscular transmission was measured using electromyography. RESULTS: The heart rate was significantly lower in group C2 (50.2 +/- 6.8 bpm) and in group C4 (54.3 +/- 11 bpm) than in the pancuronium group (62.4 +/- 13.2 bpm) 3 min after induction of anaesthesia and until 60 min after induction. None of the other haemodynamic parameters showed any difference between groups. Onset time was 5.22 +/- 3.43 min in group P, 6.42 +/- 2.1 min in group C2 and 2.92 +/- 1.2 min in group C4. CONCLUSION: Under high-dose opioid induction, bradycardia must be considered if cisatracurium is administered to cardiac surgery patients.

Adolescent↗
PubMed2001

[Ultrasonography and peridural anesthesia. Technical possibilities and limitations of ultrasonic examination of the epidural space].

Epidural anaesthesia (EA) is the most important analgesia technique in obstetrics for delivery. In pregnancy, hormonal adjustments lead to an alteration of tissue consistency, which often causes an early, untimely loss of resistance. Apart from mere inspection and palpation, no useful diagnostic method prior to EA performance has been established yet. In this prospective study, we examined 100 pregnant women, who had been admitted for childbirth and were undergoing epidural block (level L3-L4) for delivery. Sonotopography of the lumbar epidural structures was performed directly before epidural puncture and childbirth. We evaluated the visibility of all anatomical structures and compared all distances measured by ultrasonography and during puncture. The correlation between distances measured by ultrasound and by puncture needle was high (r2 = 0.79). No obvious dependency was found between ultrasonic and puncture angle (r2 = 0.19). The temporal distance from ultrasonic examination and puncture causes unavoidable differences: each deviation between ultrasound and puncture conditions causes a modification of the puncture depth. The patient acceptance of the procedure was very good. Ultrasonography offers the possibility to determine site and direction of epidural puncture and distance of the epidural space to the skin even before the puncture attempt. The ultrasound controlled EA for delivery can easily be inserted into the clinical routine. Ultrasonography can fill an important diagnostic gap in regional anaesthesia.

Adult↗
PubMed2001

[Peripheral nerve block. An overview of new developments in an old technique].

General anaesthesia and peripheral neuronal blockade are techniques which were introduced into clinical practice at the same time. Although general anaesthesia was accepted significantly faster due to effective new drugs and apparent ease of handling, neuronal blockade has recently gained great importance. The reasons are in particular newer aids such as industrially produced catheter sets, nerve stimulators and ultrasound guidance which have facilitated that these economical techniques can be used not only for intraoperative anaesthesia but also for perioperative analgesia without any major risks for the patients. In parallel to epidural anaesthesia a change of paradigms has recently taken place using catheter instead of single-shot techniques. This allows the loading dose of the local anaesthetics to be installed in a safe way, to reload the dose when intraoperatively required and to extend the analgesia perioperatively by this technique using lower concentrations of the same drugs or drug combinations. A great number of short, middle or long acting local anaesthetics are available to choose the right drug for any particular case. Short and middle acting drugs are characterised by a faster onset compared to long acting drugs, but toxic plasma levels are seen during long time application causing seizures or drowsiness or by using prilocaine methemoglobin. Therefore long acting local anaesthetics such as bupivacaine, ropivacaine or levobupivacaine are the first choice drugs for long time application via peripheral nerve catheters for perioperative anaesthesia and analgesia. By using low concentrations of these potent drugs even for a longer period of time, no toxic plasma levels are seen with the exception of artificial intravasal injections. Additives such as opioids and alpha 2-sympathomimetics are also used. While the use of opioids is controversial, alpha 2-sympathomimetics are able to accelerate the onset and to extend the duration of regional anaesthesia and analgesia.

Animals↗
PubMed2001

Influence of N-acetylcysteine on hepatic amino acid metabolism in patients undergoing orthotopic liver transplantation.

Experimental treatment with the antioxidant and glutathione precursor N-acetylcysteine (NAC) has been performed in orthotopic liver transplantation (OLT) to reduce reperfusion injury. To investigate the effect of NAC on the hepatic and intestinal amino acid metabolism, intraoperative amino acid exchange rates were studied in liver transplant recipients with high dose NAC treatment (n = 10) and in control patients (n = 9). Treatment with NAC was found to cause a loss of amino acids and increased urea nitrogen release from the liver graft. The net balance of most amino acids was shifted to increased hepatic release or decreased hepatic uptake. The initial cumulative splanchnic release of all proteinogenic amino acids in the NAC treated group was significantly higher than in the control group. These findings are tentatively explained by an increased net protein catabolism in the liver. The increased hepatic urea and glutamine production rate of the NAC treated patients is expected to increase the energy and oxygen demand of the liver in this critical situation. Thus, NAC may have caused marked metabolic disturbances in the freshly implanted graft. The dosage of NAC should therefore be modified to avoid these disadvantages.

Acetylcysteine↗
PubMed2001

Cerebral venous thrombosis in childhood.

This was a retrospective study to determine different etiologies of cerebral venous thrombosis (CVT) in childhood and to correlate extent and location of thrombosis with the etiology and the age of the child as well as the final outcome. In addition, the radiologic approach is discussed. This was a retrospective analysis of 19 children with CVT. The children were examined by contrast-enhanced dynamic CT. Radiologic findings were correlated with the etiology of CVT. Cerebral venous thrombosis is not as infrequent in children as has been thought. Cerebral venous thrombosis in children can occur due to trauma (n=9), infections (n=7), or coagulation disorders (n=3). Extent and location of thrombosis, as well as complications, final outcome, and therapy, depend on the etiology. Computed tomography remains a valuable primary imaging modality in the diagnosis of CVT in the acutely injured or diseased child.

Child↗
PubMed2001

Butyrylcholinesterase-Mediated enhancement of the enzymatic activity of trypsin.

1. Acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BuChE, EC 3.1.1.8) are enzymes that catalyze the hydrolysis of esters of choline. 2. Both AChE and BuChE have been shown to copurify with peptidases. 3. BuChE has also been shown to copurify with other proteins such as transferrin, with which it forms a stable complex. In addition, BuChE is found in association with beta-amyloid protein in Alzheimer brain tissues. 4. Since BuChE copurifies with peptidases, we hypothesized that BuChE interacts with these enzymes and that this association had an influence on their catalytic activities. One of the peptidases that copurifies with cholinesterases has specificity similar to trypsin, hence, this enzyme was used as a model to test this hypothesis. 5. Purified BuChE causes a concentration-dependent enhancement of the catalytic activity of trypsin while trypsin does not influence the catalytic activity of BuChE. 6. We suggest that, in addition to its esterase activity, BuChE may assume a regulatory role by interacting with other proteins.

Acetylcholinesterase↗
PubMed2001

Etomidate and thiopental inhibit platelet function in patients undergoing infrainguinal vascular surgery.

BACKGROUND: Postoperative platelet hyperaggregability following general anesthesia has been reported in patients undergoing major vascular surgery. In contrast, since anesthetic agents inhibited platelet function both in vitro and in vivo, an increased risk for postoperative bleedings due to prolonged platelet dysfunction has been discussed. Nevertheless, data describing platelet-affecting properties of induction agents such as etomidate and thiopental in patients undergoing major vascular surgery are lacking. METHODS: Platelet function was determined at 0, 2, 20, and 200 microg/ml thiopental and at 0, 0.2, 2, 20 microg/ml etomidate in vitro in blood samples drawn from 16 patients suffering from severe occlusive arterial disease. In addition, 30 patients undergoing vascular surgery were investigated before (PRE) and after anesthesia induction (T0) either with etomidate (ETO group, n=16) or thiopental (THIO group, n=14), and 2 h after the beginning of surgery (T2). Platelet function was determined according to platelet aggregation, in vitro bleeding time, and flow cytometric measurements. RESULTS: In vitro, P-selectin expression was inhibited by etomidate at 2 and 20 microg/ml (-28% and -38%, respectively) and also by thiopental at 200 microg/ml (-27%). In patients undergoing vascular surgery, anesthesia induction in the ETO group resulted in a 31% prolongation of the in vitro bleeding time and an inhibition of ADP- and collagen-induced platelet aggregation (-30% and -17%, respectively) and of P-selectin expression (-25%) at T0. In the THIO group, only ADP-induced platelet aggregation was affected (-16%). At T2, all parameters had reached PRE level again in both groups. Furthermore, in comparison with the THIO group, operation time was significantly prolonged and transfusion volume was significantly increased in the ETO group. In addition, platelet count and hematocrit significantly decreased at T2, whereas levels of tPA, PAI-1, fibrinogen and antithrombin III and partial thromboplastin time remained unchanged in both groups during the study period. CONCLUSIONS: In the present study, etomidate and, to a minor extent, thiopental offered significant platelet inhibitory properties. Anesthetic-induced platelet inhibition may lead to higher transfusion rates and prolonged operation times. Therefore, anesthetic-related platelet inhibitory properties should be considered when searching for the anesthetic agent of choice, especially in patients with compromised hemostasis and co-existing bleeding disorders.

Aged↗
PubMed2001

Ultrasound control for presumed difficult epidural puncture.

BACKGROUND: The efficacy of epidural anaesthesia depends on the accurate identification of the epidural space (ES). Abnormal anatomical conditions may make the procedure difficult or impossible. The aim of this study was to investigate whether pre-puncture ultrasound examination of the spinal anatomy might be beneficial in expected cases of difficult epidural anaesthesia. METHODS: We used digital ultrasound equipment with a 5-MHz transducer to assess the anatomy of the ES and the posterior parts of the spinal column. We examined 72 parturients with abnormal anatomical conditions who were scheduled for epidural anaesthesia. The women were randomised into two equal groups. In all patients, the standard loss of resistance technique was used. In the ultrasound group, an ultrasound examination of the appropriate spinal region was conducted prior to epidural puncture. ES depth seen on the ultrasound images was compared to the ES depth measured by the needle. We compared the number of puncture attempts with the standard method (control group) to the number of attempts under ultrasound guidance. RESULTS: Ultrasonography significantly improved operating conditions for epidural anaesthesia. The maximum VAS scores and patient acceptance were significantly better. CONCLUSIONS: With ultrasound measurement of the ES depth, the quality of epidural anaesthesia was enhanced.

Adult↗