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H Hecker

Publications and source records attributed to H Hecker.

At least 37 records · Page 2Linked to original sources
PubMed2002

Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients.

BACKGROUND: Patients with metastatic colorectal cancer are usually offered systemic chemotherapy as palliative treatment. A multivariate analysis was performed in order to identify predictors and their constellation that allow a valid prediction of the outcome in patients treated with 5-fluorouracil (5-FU)-based therapy. PATIENTS AND METHODS: A total of 3825 patients treated with 5-FU within 19 prospective randomised and three phase II trials were separated into learning (n = 2549) and validation (n = 1276) samples. Data were analysed by tree analysis using the recursive partition and amalgamation method (RECPAM). A predictor could only enter the RECPAM analysis if the number of patients with missing values was < 33.3% within a node, and the minimal node size was set to 50 patients. Twenty-three potential predictors were grouped into subsets of laboratory variables (11 parameters), tumour-related variables (seven parameters) and clinical variables (five parameters). In the first step, tree analysis was performed separately for each predictor subset. The selected prognostic parameters of the resulting partial models (the 'winners') were entered into the general model. The classification rule from the data of the learning set was applied to the independent validation set. RESULTS: Winners of the subgroup analysis for laboratory variables were: platelets > or = 400 x 10(9)/l, alkaline phosphatase > or = 300 U/l, white blood cell (WBC) count > or = 10 x 10(9)/l and haemoglobin < 11 x 10(9)/l, and all predicted a worse outcome. Negative predictors within the subgroup of tumour parameters were: number of tumour sites more than one or more than two, presence of liver metastases or peritoneal carcinomatosis, which predicted a worse outcome. Furthermore, presence of lung metastases, a primary rectal cancer and presence of lymph node metastases all predicted a better outcome in the multivariate setting. Among the clinical parameters only performance status of ECOG 0 or 1 predicted better outcome. In the final regression tree, three risk groups could be identified: low risk group (n = 1111) with a median survival of 15 months for patients with ECOG 0/1 and only one tumour site; intermediate risk group (n = 904) with a median survival of 10.7 months for patients with ECOG 0/1 and more than one tumour site and alkaline phosphatase < 300 U/l or patients with ECOG > 1, WBC count < 10 x 10(9)/l and only one tumour site; high risk group (n = 534) with a median survival of 6.1 months for patients with ECOG 0/1 and more than one tumour site and alkaline phosphatase of > or = 300 U/l or patients with ECOG > 1 and more than one tumour site or WBC count > 10 x 10(9)/l. The median survival times for the good, intermediate and high risk groups in the validation sample were 14.7, 10.5 and 6.4 months, respectively. CONCLUSIONS: Patients can be divided into at least three risk groups depending on the four baseline clinical parameters: performance status, WBC count, alkaline phosphatase and number of metastatic sites. Any molecular or biological marker should be validated against these clinical parameters and decisions for more or less intensive treatments may be studied separately in these three risk groups. Also, clinical trials should be stratified according to the three risk groups.

Alkaline Phosphatase↗
PubMed2001

Incidence of metachronous testicular cancer in patients with extragonadal germ cell tumors.

BACKGROUND: The frequency of subsequent testicular cancer (referred to as metachronous testicular cancer) in men who have had previous testicular cancer is relatively high. The rate of metachronous testicular cancer in men with extragonadal germ cell tumors (EGCTs), however, is largely unknown. We conducted a retrospective study of EGCT patients to determine the incidence, cumulative risk, and specific risk factors for metachronous testicular cancers. METHODS: A standardized questionnaire about patient characteristics, the extent of EGCT disease, any second malignancies, and treatments received was completed for 635 patients with EGCTs identified from the medical records of 11 cancer centers in Europe and the United States from 1975 through 1996. Comparisons with age group-specific data from the Saarland, Germany, population-based cancer registry were used to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to analyze survival data and cumulative risk. All statistical tests were two-sided. RESULTS: Sixteen EGCT patients (4.1%) developed metachronous testicular cancers, with a median time between diagnoses of 60 months (range, 14-102 months). The risk of developing metachronous testicular cancers was statistically significantly increased in patients with EGCTs (observed = 16; expected = 0.26; SIR = 62; 95% confidence interval [CI] = 36 to 99) and in subsets of EGCT patients with mediastinal location (SIR = 31; 95% CI = 8 to 59), retroperitoneal location (SIR = 100; 95% CI = 54 to 172), and nonseminomatous histology (SIR = 75; 95% CI = 43 to 123). The cumulative risk of developing a metachronous testicular cancer 10 years after a diagnosis of EGCT was 10.3% (95% CI = 4.9% to 15.6%) and was higher among patients with nonseminomatous EGCTs (14.3%; 95% CI = 6.7% to 21.9%) and retroperitoneal EGCTs (14.2%; 95% CI = 5.6% to 22.8%) than among patients with seminomatous EGCTs (1.4%; 95% CI = 0.0% to 4.2%) and mediastinal EGCTs (6.2%; 95% CI = 0.1% to 12.2%). CONCLUSIONS: Patients with EGCTs, particularly those with retroperitoneal or nonseminomatous tumors, but also those with primary mediastinal EGCTs, are at an increased risk of metachronous testicular cancer.

Adolescent↗
PubMed2001

Phenol derivatives accelerate inactivation kinetics in one inactivation-deficient mutant human skeletal muscle Na(+) channel.

Altered inactivation kinetics in skeletal muscle Na(+) channels due to mutations in the encoding gene are causal for the alterations in muscle excitability in nondystrophic myotonia. Na(+) channel blockers like lidocaine and mexiletine, suggested for therapy of myotonia, do not reconstitute inactivation in channels with defective inactivation in vitro. We examined the effects of four methylated and/or halogenated phenol derivatives on one heterologously expressed inactivation-deficient Paramyotonia congenita-mutant (R1448H) muscle Na(+) channel in vitro. All these compounds accelerated delayed inactivation of R1448H-whole-cell currents during a depolarization and delayed accelerated recovery from inactivation. The potency of these effects paralleled the potency of the drugs to block the peak current amplitude. We conclude that the investigated phenol derivatives affect inactivation-deficient Na(+) channels more specifically than lidocaine and mexiletine. However, for all compounds, the effect on inactivation was accompanied by a substantial block of the peak current amplitude.

Cell Line↗
PubMed2001

Attention deficits in minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (HE) is characterized by a decrease of psychomotor speed, and deficits in visual perception, visuo-spatial orientation, and visuo-constructive abilities. Attention deficits have also been proposed to be part of the syndrome. Several attempts were made in the past to elaborate suitable psychometric means for the assessment of minimal HE. However, there is still no "gold standard" for the diagnosis of minimal HE. We recently evaluated the so called "PSE-Test" for the assessment of minimal HE, a test battery which does not include a test predominantly aimed at the assessment of attention. We therefore presented a battery of attention tests in addition to the PSE-Test to a group of cirrhotics without clinical signs of HE compared to a healthy control group matched for age and education to determine whether the addition of special attention tests would increase the diagnostic sensitivity of the PSE-Test. It was shown that the patients with a pathological PSE-Test result differed significantly from controls in all attention tests applied, while the patients with normal PSE-Test results achieved attention test results similar to that of the controls. Thus, the PSE-Test results represent attention deficits as well as deficits in motor skills, visuo-spatial orientation, and visual construction.

Adult↗
PubMed2001

[Analgesic dosage with (S)-ketamine/propofol vs. (S)-ketamine/midazolam: sedation, stress response and hemodynamics--a controlled study of surgical intensive care patients].

OBJECTIVE: The study was undertaken to investigate the influence of two different regimens of analgosedation on control and quality of sedation, stress response and haemodynamic parameters. METHODS: After ethical approval, 30 surgical intensive care patients were investigated in an open, controlled design. Patients with initial cardiocirculatory stability received 0.33-1.0 mg/kg BW/h (S)-ketamine together with 1-3 mg/kg BW/h propofol (SK/P-group), whereas patients with impaired cardiocirculatory stability received 0.33-1.0 mg/kg BW/h (S)-ketamine and 0.033-0.1 mg/kg BW/h midazolam (SK/M-group). Analgosedation was titrated until tolerance of respirator treatment was achieved and the patient was asleep, but able to respond to simple commands. At least 12 h after beginning of analgosedation, a simple neurological examination ("diagnostic window") was undertaken. RESULTS: In both groups, biometric data and diseases were altogether comparable, and tolerance of respirator treatment was excellent. About 16 h after start of analgosedation, 13 of 14 patients (93%) in the SK/P-group were immediately cooperative. In 2 of 16 patients of the SK/M-group, self extubation occurred, and 9 of 14 remaining patients (64%) were immediately cooperative (p = 0.065). Assessment of control and quality of analgosedation indicated slight advantages in SK/P-patients. SEF90 showed predominant beta-activity in both collectives, which increased in the course of time. Adrenaline, noradrenaline, ADH, ACTH and cortisol were measured at 7 time points. All endocrine stress parameters were consistently above normal range, but decreased during the observation period (p < 0.05). In the SK/M-group, ADH was significantly and noradrenaline initially higher than in controls. Systolic arterial pressure was comparable, whereas heart rate was significantly lower in the SK/P-group (p = 0.001). No relevant changes of endocrine or haemodynamic parameters were observed at neurological examination. CONCLUSION: In surgical intensive care patients, analgosedation with SK/P showed some advantages over SK/M with respect to control and quality. The endocrine stress response was reduced by both regimens in course of time. Altogether higher levels of ADH and noradrenaline during SK/M-analgosedation let expect higher cardiocirculatory stability and possible reduction of catecholamine demand. Due to ketamine-typical beta-activity, a reliable assessment of sedation by the pEEG is not possible.

Adrenocorticotropic Hormone↗
PubMed2001

Detection of the apical lesion and the mandibular canal in conventional radiography and computed tomography.

OBJECTIVE: The purpose of this study was to compare the information gathered from dental radiography and high resolution computed tomography (CT) scans with regard to the detection of the endodontic lesion and its relation to the important neighboring anatomic structures such as the mandibular canal. STUDY DESIGN: Fifty patients with a persistent apical lesion referred for endodontic surgery were selected. The teeth involved were 6 mandibular premolars and 44 mandibular molars. Eighty roots were evaluated. For each case 1 CT scan and 1 periapical radiograph were taken. The apical lesion and the mandibular canal were evaluated for possible identification in CT scan or radiograph. The presence of the lesion was correlated to the findings during the surgical procedure. The CT scans of the involved roots were further evaluated with regard to the bone thickness and differentiation between cancellous and cortical bone. The position of the lesion/root within the mandible was studied in all dimensions. RESULTS: All 78 lesions diagnosed during surgery were also visible with the CT scan. In contrast, only 61 of the lesions were noted by conventional radiographs. The mandibular canal could be identified in 31 cases in dental radiographs, whereas in the oblique cuts of the corresponding CT scans the mandibular canal was detected in all patients. The amount of cortical and cancellous bone and the bone thickness as well as the three-dimensional extent of the lesion could only be adequately interpreted in CT scans. CONCLUSIONS: The use of CT provides additional, beneficial information not available from dental radiographs for treatment planning in apical surgery of mandibular premolars and molars. When the mandibular canal cannot be detected in dental radiographs or is in close proximity to the lesion or root apex, CT should be considered before endodontic surgery. The presence, extent, and location of the lesion and its relation to the mandibular canal can be predictably evaluated in a CT scan of the area.

Adult↗
PubMed2001

Propofol blocks human skeletal muscle sodium channels in a voltage-dependent manner.

UNLABELLED: Propofol decreases muscle tone in the absence of neuromuscular blocking drugs. This effect probably cannot be attributed solely to central nervous depression. We studied the effects of propofol on heterologously expressed skeletal muscle sodium channels. Our hypothesis was that the decrease in muscle tone may partly be attributed to an interaction of propofol with sarcolemmal sodium channels. Cells were voltage clamped and whole-cell sodium inward currents were recorded in the absence and presence of propofol. When depolarizing pulses to 0 mV were started from a holding potential close to the normal resting potential of muscle (-70 mV), or when a 2.5-s prepulse inducing slow inactivation was applied before the test pulse at -100 mV, a significant reduction in the peak current amplitude was achieved by 10 and 5 microM propofol, respectively (P < 0.001). Half-maximum blocking concentrations with these protocols were 23 and 22 microM. Blocking potency increased at depolarized membrane potentials with the fraction of inactivated channels; the estimated dissociation constant K(d) from the inactivated state was 4.6 microM. These results suggest that propofol significantly blocks sarcolemmal sodium channels at clinically relevant concentrations while maintaining potentials close to the physiological resting potential. IMPLICATIONS: Voltage-gated sodium channels mediate the initiation and propagation of action potentials along the sarcolemma. Results from our study show that those channels are targeted and blocked in a concentration- and voltage-dependent manner by propofol. This mechanism may contribute to the reduction in muscle excitability.

Action Potentials↗
PubMed2000

Hepatocyte growth-factor-scatter factor can stimulate post-operative tumor-cell proliferation in childhood hepatoblastoma.

Rapid growth of residual tumor after partial hepatectomy has been observed during the period of liver regeneration in children with malignant embryonal hepatoblastoma. The aim of this study was to elucidate the role of hepatocyte growth-factor-scatter factor (HGF-SF) in this phenomenon. Markedly increased serum levels of HGF-SF up to 15 ng/ml were found in 13/18 patients after liver resection and in 6/16 patients with regressive tumors after chemotherapy, in comparison with 15 patients with non-pre-treated hepatoblastoma and 20 healthy children of the same age group. In the tumors, epithelial tumor cells highly expressed the HGF-SF receptor c-met, as shown by immunohistochemistry and m-RNA RT-PCR. The hepatoblastoma cell lines HepT1, HepT3 and HUH6 reacted with significantly increased proliferation to rhHGF-SF in these concentrations (1-15 ng/ml). In the tumors, HGF-SF was found to be expressed in the stromal fibroblasts. In culture, hepatoblastoma cells (HepT3, HUH6) stimulated secretion of the factor by human fibroblasts, indicating the paracrine fashion of intratumoral HGF-SF production. Cultured hepatoblastoma cells ceased to proliferate at 20-50 ng/ml HGF-SF, and they underwent cell death at >/=100 ng/ml. In contrast, the hepatocellular-carcinoma cell line HepG2 decreased growth under HGF-SF in a dose-dependent manner. We conclude that post-operatively secreted and intratumorally produced HGF-SF can function as a growth factor for hepatoblastoma, while the same agent has a cytostatic effect in unphysiologically high concentrations.

Cell Division↗
PubMed2000

Voltage-dependent blockade of normal and mutant muscle sodium channels by benzylalcohol.

1. We studied the effects of benzylalcohol on heterologously expressed wild type (WT), paramyotonia congenita (R1448H) and hyperkalaemic periodic paralysis (M1360V) mutant alpha-subunits of human skeletal muscle sodium channels. 2. Benzylalcohol blocked rested channels at -150 mV membrane potential, with an ECR(50) of 5.3 mM in wild type, 5.1 mM in R1448H, and 6.2 mM in M1360V. When blockade was assessed at -100 mV, the ECR(50) was reduced in R1448H (2 mM) compared with both wild type (4.3 mM; P<0.01) and M1360V (4.3 mM). 3. Membrane depolarization before the test depolarization significantly promoted benzylalcohol-induced sodium channel blockade. The values of K(D) for the fast-inactivated state derived from benzylalcohol-induced shifts in steady-state availability curves were 0.66 mM in wild type and 0.58 mM in R1448H. In the presence of slow inactivation induced by 2.5 s depolarizing prepulses, the ECI(50) for benzylalcohol-induced current inhibition was 0.59 mM in wild type and 0.53 mM in R1448H. 4. Recovery from fast inactivation was prolonged in the presence of drug in all clones. 5. Benzylalcohol induced significant frequency-dependent block at stimulating frequencies of 10, 50, and 100 Hz in all clones. 6. Our results clearly show that benzylalcohol is an effective blocker of muscle sodium channels in conditions that are associated with membrane depolarization. Mutants that enter voltage-dependent inactivation at more hyperpolarized membrane potentials compared with wild type are more sensitive to inhibitory effects at the normal resting potential.

Amino Acid Substitution↗
PubMed2000

[Sympathoadrenergic, hemodynamic and stress response during coinduction with propofol and midazolam].

OBJECTIVE: This study was undertaken to investigate simultaneously the influence of coinduction with propofol and midazolam on sympathoadrenergic and hemodynamic reactions and stress response during the extended induction period of TIVA. METHODS: 2 x 20 patients over the 60th year of life with major visceral surgery were investigated in a prospective randomized design. All patients received about 0.1 mg/kg BW midazolam for oral premedication. In the midazolam-group, induction of TIVA was undertaken with 0.05 mg/kg BW midazolam, 2.5 micrograms/kg BW fentanyl and 1.0 mg/kg BW propofol (1 min later). Controls received 2.5 micrograms/kg BW fentanyl and 2.0 mg/kg BW propofol. After muscle relaxation with 0.1 mg/kg BW vecuronium, TIVA was conducted in both groups with 8-5 mg/kg BW/h propofol and bolus injections of fentanyl with respect to clinical demands. Beyond consumption of anesthetics and recovery, sympathoadrenergic and hemodynamic reactions and SEF90 were investigated at 6 time points before induction of anesthesia and at skin incision. Plasma levels of ADH, ACTH and cortisol were measured twice before induction and at skin incision. RESULTS: Biometric data of both groups were comparable, and mean age was over 65 years. In the midazolam-group, co-induction with a mean dosage of 3.8 mg midazolam halved the induction dose of propofol and reduced the propofol demand during the following course of anesthesia as well, achieving a significant over all reduction of 200 mg propofol (p = 0.04). With respect to recovery from anesthesia more than 90 min later, no significant differences were found. Plasma concentrations of noradrenaline and adrenaline dropped significantly in both groups (p < 0.0001), as well as mean arterial pressure and heart rate (Fig. 1 and 2). For ADH, ACTH, cortisol and SEF90, no statistical differences were observed. Plasma-concentrations of midazolam were significantly higher in the midazolam-group. CONCLUSION: In elderly patients, co-induction with 0.05 mg/kg BW midazolam halved the induction dose of propofol and led to a further dose reduction with maintained hypnotic potency. However, the halvage of propofol induction dose had no effect on the reduction of the sympathoadrenergic tone with decrease of blood pressure and heart rate. The overall moderation of the stress response was comparable as well. Thus, both induction regimens investigated in this study cannot be recommended in patients with severe hemodynamic disorders like hemorrhagic or cardiac shock. The propofol reduction should be primarily considered under economic aspects.

Aged↗
PubMed2000

Succinylcholine metabolite succinic acid alters steady state activation in muscle sodium channels.

BACKGROUND: Animal experiments revealed that succinylcholine produced masseter muscle rigidity and activated myotonic discharges despite neuromuscular blockade with a nondepolarizing blocker. These results suggest that either succinylcholine or its metabolites might interfere directly with voltage-operated ion channels of the sarcolemma. The aim of this study was to examine effects of one product of succinylcholine hydrolysis, succinic acid, on voltage-gated muscle sodium (Na+) channels. METHODS: Alpha subunits of human muscle sodium channels were heterologously expressed in HEK293 cells. Activation of Na+ currents was examined applying standard whole-cell voltage-clamp protocols in the absence (control and washout) and presence of succinic acid in different concentrations (0.05-10 mm). RESULTS: Succinic acid shifted the midpoints of steady state activation plots in the direction of more negative test potentials, indicating that channels open during smaller depolarizations in the presence of the drug. The maximum amount of the negative shift in 10 mm succinic acid was -6.3 +/- 1.7 mV; the EC50 for this effect was 0.39 mm. In addition, succinic acid (10 mm) significantly enhanced maximum currents after depolarizations with respect to a series of control experiments. CONCLUSION: Succinic acid facilitates voltage-dependent activation in muscle sodium channels in vitro. This might lead to muscle hyperexcitability in vivo.

Anti-Ulcer Agents↗
PubMed2000

Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6.

OBJECTIVE: To evaluate whether plasma concentrations of procalcitonin (PCT), interleukin-6 (IL-6), protein complement 3a (C3a), leukocyte elastase (elastase), and the C-reactive protein (CRP) determined directly after the clinical onset of sepsis or systemic inflammatory response syndrome (SIRS) discriminate between patients suffering from sepsis or SIRS and predict the outcome of these patients. DESIGN: Prospective study. SETTING: Medical intensive care unit at a university hospital. PATIENTS: Twenty-two patients with sepsis and 11 patients with SIRS. MEASUREMENTS AND MAIN RESULTS: The plasma concentrations of PCT, C3a, and IL-6 obtained < or =8 hrs after clinical onset of sepsis or SIRS but not those of elastase or CRP were significantly higher in septic patients (PCT: median, 16.8 ng/mL, range, 0.9-351.2 ng/mL, p = .003; C3a: median, 807 ng/mL, range, 422-4788 ng/mL, p < .001; IL-6: median, 382 pg/mL, range, 5-1004 pg/mL, p = .009, all Mann-Whitney rank sum test) compared with patients suffering from SIRS (PCT: median, 3.0 ng/mL, range, 0.7-29.5 ng/mL; C3a: median, 409 ng/mL, range, 279566 ng/mL; IL-6: median, 98 pg/mL, range, 23-586 pg/mL). The power of PCT, C3a, and IL-6 to discriminate between septic and SIRS patients was determined in a receiver operating characteristic analysis. C3a was the best variable to differentiate between both populations with a maximal sensitivity of 86% and a specificity of 80%. An even better discrimination (i.e., a maximal sensitivity of 91% and a specificity of 80%) was achieved when PCT and C3a were combined in a "sepsis score." C3a concentrations also helped to predict the outcome of patients. Based on the sepsis score, a logistic regression model was developed that allows a convenient and reliable determination of the probability of an individual patient to suffer from sepsis or SIRS. CONCLUSIONS: Our data show that the determination of PCT, IL-6, and C3a is more reliable to differentiate between septic and SIRS patients than the variables CRP and elastase, routinely used at the intensive care unit. The determination of PCT and C3a plasma concentrations appears to be helpful for an early assessment of septic and SIRS patients in intensive care.

Adult↗
PubMed2000

Disruption of intracerebral progression of C6 rat glioblastoma by in vivo treatment with anti-CD44 monoclonal antibody.

OBJECT: Glioblastoma multiforme (GBM) invasiveness is a complex process that involves recognition and attachment of GBM cells to particular extracellular matrix (ECM) molecules before migrating into proteolytically modified matrix and inducing angiogenesis. The CD44 molecule, which is a transmembrane adhesion molecule found on a wide variety of cells including GBM, has been suggested as the principal mediator of migration and invasion. The aim of the present study was to demonstrate whether an antibody specific to the standard form of CD44 (CD44s, 85-90 kD) might prevent invasion and thus disrupt progression of C6 GBM in vivo. METHODS: Immunostaining demonstrated homogeneous expression of CD44s on the surface of C6 GBM cells and tumors. Flow cytometric analysis demonstrated binding saturation of anti-CD44s monoclonal antibody (mAb) to the receptor at 1 microg/5 x 10(5) cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive (up to 94+/-2.7%; mean +/- standard deviation [SD]) detachment of C6 cells from ECM-coated culture. Blocking of CD44s in vivo resulted in significantly reduced C6 brain tumors (3.6+/-0.4% [SD])--measured as the quotient: tumor surface (mm2)/brain surface (mm2) x 100--compared with untreated (19.9+/-0.9%) or sham-treated (19.2+/-1.1 to 19.3+/-2.5% [SD]) rats. Disruption of C6 GBM progression correlated with an improved food intake; treated rats were significantly less cachectic (166.6+/-16.4 g [SD]) than those that were untreated (83+/-2.7 g [SD]) or sham-treated (83.4+/-1.1 to 83+/-2.2 g [SD]) rats. CONCLUSIONS: The authors conclude that CD44s-targeted treatment with specific mAb may represent an effective means for preventing progression of highly invasive GBMs.

Animals↗
PubMed2000

Bidirectional classification procedures: double tree and double cluster.

Partition based prediction rules as derived in CART, RECPAM or CBR, relating multivariate predictor variables X to a response variable Y, may be extended to bidirectional classification procedures. Tree or clustering algorithms are simultaneously applied to X and Y resulting in a double partition classification table that should be able to detect existing characteristic patterns of predictor and response values and relate them to each other.

Algorithms↗
PubMed1999

CD44s-targeted treatment with monoclonal antibody blocks intracerebral invasion and growth of 9L gliosarcoma.

Glioma invasiveness is a complex process involving recognition and attachment of tumor cells to particular extracellular matrix (ECM) molecules prior to migrating into proteolytically modified matrix and inducing angiogenesis. CD44 is a group of transmembrane adhesion molecules found on a wide variety of cells including gliomas that has been suggested as the principal mediator of migration/invasion. The aim of the present study was to demonstrate whether antibody specific for the standard form of CD44 (CD44s, 85-90 kDa) might prevent invasion, thus blocking growth of the 9L gliosarcoma in vivo. High expression of CD44s on the surface of 9L cells and brain tumors was demonstrated by immunochemistry. Fluorescence-activated cell sorting (FACS) demonstrated binding saturation of anti-CD44s monoclonal antibody (mAb) to the receptor at 1 microg/5 x 10(5) cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive, up to 95%+/-2.5% detachment of 9L cells from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in significantly reduced 9L brain tumors (2.5%+/-0.4%)--measured as the quotient: tumor surface (mm2)/brain surface (mm2) x 100--as compared to untreated (16.1%+/-2.2%) or sham-treated rats (16%+/-3.7% to 16.1%+/-3%). We conclude that CD44s-targeted treatment with specific mAb may be an effective means for preventing glioma progression.

Animals↗
PubMed1999

[Performance of different CT angiography imaging modalities in detecting renal artery stenoses].

PURPOSE: Purpose of the study was to compare the sensitivity and specificity of various display modalities in the detection of renal artery stenosis. In particular, the difference between hard-copy reading and interactive analysis at the workstation was assessed. MATERIALS AND METHODS: Selected patients (n = 31) with expected suboptimal conditions for CT angiography due to long-standing hypertension and compromised renal function were included. Six radiologists evaluated independently a total of 77 renal arteries with 49 renal artery stenoses proven by angiography. Image analysis included: mode A: interactive display, analysis of multiplanar reformats and axial sections at the workstation, mode B: visualization of MIPs in the coronal and axial planes as hard copies only, mode C: visualization of MIPs and axial sections as hard copies only. RESULTS: The following sensitivities and specificities were found for internal readers and (readers from outside institutions): mode A: 94.8%, 87.9%, mode B: 97.7% (95.1%), 80.3% (75.4%); mode C: 97.0% (95.3%), 78.8% (76.6%). The differences were statistically not significant (p > 0.05). CONCLUSIONS: Standardized hard copies of MIPs plus axial CT provide sufficient accuracy to detect renal artery stenosis compared to interactive imaging even in this highly selected group of patients.

Adult↗
PubMed1998

Increased susceptibility to postoperative sepsis in patients with impaired monocyte IL-12 production.

IL-12 is a potent immunoregulatory cytokine that is essential for the development of protective immunity, as demonstrated by numerous animal models of infection. Here, we provide evidence for a critical role of IL-12 in human sepsis. The results of a prospective study of 184 patients undergoing major elective surgery of the upper and lower gastrointestinal tract revealed that, in contrast to patients showing uneventful recovery, monocyte IL-12 production was severely and selectively impaired in patients developing postoperative sepsis. Moreover, the extent of monocyte IL-12 suppression correlated with the severity of postoperative sepsis. Monocyte IL-12 secretion was suppressed before surgery and remained low until the onset of sepsis. Therefore, the suppression of IL-12 secretion preceded the onset of postoperative sepsis but did not occur as a consequence of major surgery. In contrast, IL-1beta production was only reduced during the late postoperative course in patients developing postoperative sepsis, and TNF-alpha release was even increased at different time intervals before the onset of sepsis. Thus, reduced IL-12 release does not reflect a general defect in monocyte cytokine production. Consequently, these results establish a critical role for IL-12 in early resistance to postoperative infection and may allow for the development of novel therapeutic strategies designed to stimulate host defense mechanisms and to reduce the incidence and severity of septic complications.

Aged↗