PubMed Health⌕ Search

Biomedical subjects

H Hecker

Publications and source records attributed to H Hecker.

At least 19 recordsLinked to original sources
PubMed2003

[Anaesthesia for caesarean section. Comparison of two general anaesthetic regimens and spinal anaesthesia].

OBJECTIVES: The study was undertaken to compare different anaesthetic techniques for scheduled or urgent caesarean section with respect to maternal circulatory parameters, maternal and fetal endocrine stress response, fetal vitality parameters and further clinical parameters such as recovery and analgesic demand. METHODS: After ethical approval,patients scheduled for general anaesthesia were randomly allocated to the esketamine group ( n=21; induction with 0.5 mg/kg BW esketamine and 1.5 mg/kg BW methohexitone, ventilation until cord cutting with FiO(2) 1.0) and the sevoflurane-group ( n=21; induction with 1.5-2.0 mg/kg BW methohexitone, ventilation until uterotomia with N(2)O/O(2) [FiO(2) 0,5] and endtidal sevoflurane concentrations about 1.0 vol%). After fetal development, all patients received 2.5 microg/kg BW fentanyl and sevoflurane (about 1.0 vol% endtidal) during ventilation with N(2)O/O(2) (FiO(2) 0.33). As a further control, a group with spinal anaesthesia ( n=22; 2.6-3.0 ml isobaric bupivacaine 0.5 %) was investigated. Maternal circulatory and endocrine plasmatic stress parameters were investigated at five time points and fetal parameters once after development.alpha< or =0.05 was considered significant. RESULTS: Biometric data were comparable in all groups. Systolic arterial pressure was higher in the esketamine group ( p=0.008), whereas the heart rate was lower during spinal anaesthesia ( p<0.001). Plasma noradrenaline decreased in all collectives ( p<0.001) and mean group levels of noradrenaline ( p=0.04) and adrenaline ( p<0.001) were lower during spinal anaesthesia. In all groups, antidiuretic hormone (ADH) remained within the normal range or was slightly increased. Adrenocorticotropic hormone (ACTH) initially increased in all groups and decreased in later time course ( p<0.001). Cortisol increased in all groups ( p<0.001) but group levels were lower during spinal anaesthesia ( p<0.001). In the groups with general anaesthesia, no significant differences in recovery times were obvious, and neither recall nor dream reactions were observed. Postoperative hypoxic incidents (psaO(2) <90%) were comparable between the groups. After spinal anaesthesia, first analgesic demand was later than in the controls ( p=0.001), and the total amount of piritramide was lower ( p=0.02). Nausea and vomiting were more frequent during spinal anaesthesia ( p=0.03). All patients were content with their regimen. Apgar scores, pH-values and adrenaline, noradrenaline and cortisol in plasma were comparable in all groups of children (69 children, 5 gemini). The fetal concentration of esketamine (251 ng/ml) was lower than the corresponding maternal values (493 ng/ml). CONCLUSIONS: When compared with methohexitone, sevoflurane and N(2)O for caesarean section, initial total intravenous anaesthesia with esketamine and methohexitone mediated specific antinociception without negative maternal or fetal effects and not taking invasion kinetics or elimination between uterotomia and cord cutting into consideration. Avoidance of N(2)O allows optimal oxygenation of the fetomaternal unit. Stress protection and hemodynamic responses were well balanced, and intraoperative recall or negative dream reactions were lacking. Superior postoperative pain protection was advantageous after spinal anaesthesia, but in contrast, nausea and vomiting were more frequent in this group.

Adult↗
PubMed2002

Hydroxyethyl starch and modified fluid gelatin maintain plasma volume in a porcine model of septic shock with capillary leakage.

OBJECTIVE: To compare the effects of different volume replacement therapies on maintenance of plasma volume in septic shock and capillary leakage syndrome. DESIGN AND SETTING: Prospective randomized, controlled animal laboratory study in a university animal laboratory. MEASUREMENTS AND RESULTS: Twenty-five fasted, anaesthetized, mechanically ventilated and multi-catheterized pigs (20.8+/-1.8 kg) received 1 g/kg body weight faeces into abdominal cavity to induce sepsis and were observed over 8 h. Five animals each received volume replacement therapy with modified fluid gelatin 4% or 8% (MFG4%, MFG8%), 6% HES 200/0.5, or Ringer's solution and were compared to controls receiving 6% HES 200/0.5. Infusion rate was titrated to maintain a central venous pressure of 12 mmHg. Plasma volume was determined using (51)Cr-labelled erythrocytes and standard formulae. Albumin escape rate was calculated using technetium (99m)Tc-labelled albumin. Colloid osmotic pressure, systemic haemodynamics and oxygenation were obtained before and 4 and 8 h after induction of sepsis. Plasma volume was reduced in the Ringer's solution group (-46%) but was maintained in HES (+/-0%), MFG4% (+4%), MFG8% (+23%) groups. Albumin escape rate increased in HES (+52%), MFG4% (+47%), MFG8% (+54%) and the Ringer's solution group (+41%) compared to controls. CONCLUSION: In this porcine septic shock model with concomitant capillary leakage syndrome, confirmed by an increased albumin escape rate, the artificial colloids HES, MFG4%, and MFG8% maintained plasma volume and colloid osmotic pressure. These results suggest the intravascular persistency of artificial colloids in the presence of albumin leakage. An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-002-1283-9)

Albumins↗
PubMed2002

Postoperative pain management in orthopaedic patients: no differences in pain score, but improved stress control by epidural anaesthesia.

BACKGROUND AND OBJECTIVE: To investigate the interactions of postoperative pain and endocrine stress response, three groups of 21 patients each with total knee arthroplasty were compared in a randomized, prospective design. For postoperative pain management, a three-in-one block, an epidural catheter analgesia or an intravenous patient-controlled analgesia was used. METHODS: After standardized balanced anaesthesia, the pain intensity was measured by a visual analogue scale (VAS). For detection of epinephrine, norepinephrine, antidiuretic hormone, adrenocorticotropic hormone and cortisol in the plasma, blood samples were taken at six time points before and up to 180 min after the start of pain therapy. In addition, systolic arterial pressure, heart rate, partial arterial oxygen saturation, nausea, vomiting and satisfaction of the patients were recorded. RESULTS: Within 15 min after the start of pain therapy, VAS in all groups was similarly reduced from >40 mm to a range <10 mm (P < 0.001). Initially, all endocrine stress variables exceeded the normal range. Epidural anaesthesia led to a significant decrease of epinephrine and norepinephrine concentrations, while an increase was observed in the group with patient-controlled analgesia, and the decrease in patients with the three-in-one block was less than in patients receiving epidural anaesthesia (P = 0.001). Differences in antidiuretic hormone, adrenocorticotropic hormone and cortisol were less pronounced. Systolic arterial pressure decreased significantly in all groups, particularly in patients with epidural anaesthesia. Partial arterial oxygen saturation and the incidence of nausea and vomiting were comparable. All patients were satisfied with the methods used. CONCLUSIONS: All methods of pain management led to sufficient analgesia, but they were not accompanied by an adequate reduction in endocrine stress response. Thus, postoperative pain is only a secondary stressor and sufficient analgesia with subjective well-being does not prove a stress-free state. With regard to the reduction of sympathoadrenergic stress response, epidural anaesthesia is superior to the three-in-one block and patient-controlled analgesia. Epidural anaesthesia is recommended particularly for high-risk patients with hypertension, coronary heart disease and diabetes mellitus. In these patients, the reduction of a 'hidden' endocrine stress response in addition to prevention of pain is of special interest.

Aged↗
PubMed2002

Diagnosis of systemic Candida infections in patients of the intensive care unit. Significance of serum antigens and antibodies.

The combined detection of Candida antigen and antibody for the determination of systemic Candida infections (SCI) was investigated. One hundred and four patients from the intensive care unit (ICU) were analysed. Seventeen of the patients were suspected of having SCI, based on clinical and laboratory criteria. In these patients, Candida antigens and antibodies were analysed extensively. Ten patients had a positive Candida antigen (titre >1:16) determined by the latex agglutination assay Cand-Tec(R) and their median antibody titre was 1:160 in the indirect haemagglutination test (HAT). Seven antigen-negative patients had a median titre of 1:1280 (HAT). Forty-one of 42 colonized control patients had negative antigen titres and a median antibody titre of 1:160. The sensitivities and specificities were 58.8% and 97.6% for antigenemia, and 52.9% and 85.7% for antibody detection. These values reached 100.0% and 83.3%, respectively, when the results of both tests were combined. This indicates a high degree of concordance between serological results (Candida antigen and/or antibodies) and clinical presentation. We conclude, that the combined investigation of antigen and antibody titres might be a helpful tool in the characterization of SCI in ICU patients, if antigen titres are >or=1:16 or antibody titres (HAT) are >or=1:640.

Adolescent↗
PubMed2002

[Co-maintenance with propofol and midazolam: sympathoadrenergic reactions, hemodynamic effects, stress response, EEG and recovery].

OBJECTIVE: The study was undertaken to investigate the influence of TIVA with propofol, midazolam and fentanyl (comaintenance, COM-group) or TIVA with propofol and fentanyl (control-group) on sympathoadrenergic and hemodynamic reactions, stress response, EEG and recovery. METHODS: After ethical approval, 2 x 20 patients of ASA-risk I - III over 55 years of age undergoing visceral surgery were investigated in a prospective randomized design. For induction of anesthesia, patients of the COM-group received 0,05 mg/kg BW midazolam und 1,0 mg/kg BW propofol, and anesthesia was maintained with 0,05 mg/kg BW/h midazolam (until 15 - 30 min before the end of the operation) together with propofol in decreasing doses of 10 - 5 - 2 mg/kg BW/h. In the control-group, 2,0 mg/kg BW propofol were used for induction followed by decreasing doses of 10 - 5 - 2 mg/kg BW/h as well. Premedication (0,1 mg/kg BW midazolam orally) and weight-dependent doses of fentanyl (2,5 microgram/kg BW for induction, 1,25 microgram/kg BW 2 min before skin incision, further repetition doses of 1,25 - 2,5 microgram/kg/BW as required) and vecuronium were equal in both groups. Beyond consumption of anesthetics and recovery, sympathoadrenergic, other endocrine and hemodynamic reactions and SEF 90 were investigated at 7 time points before induction and postoperative recovery. alpha </= 0,05 was considered significant. RESULTS: Biometric data (mean age > 70 years) and duration of anesthesia and operation were comparable in both groups. Consumption of midazolam was higher in the COM-Group (14,8 vs. 7,5 mg; p = 0,004), whereas doses of fentanyl and vecuronium were comparable in both collectives. Recovery was significantly (p = 0,004) delayed in the COM-group: observing of simple orders 12,6 vs. 5,8 min, orientation with respect to person 19,8 vs. 9,9 min, local orientation 23,1 vs. 11,3 min. Mean arterial pressure in the COM-group was throughout lower than in the control-group, whereas heart rate was higher during the course of operation. Endocrine stress parameters (adrenaline, noradrenaline, antidiuretic hormone, adrenocorticotropic hormone, cortisol) and spectral edge frequency (SEF 90; Dräger-pEEG) were comparable in group level and time course between both groups. Plasma-concentrations of midazolam were significantly higher in the COM-group. CONCLUSION: In elderly patients undergoing visceral surgery in TIVA and when compared with propofol alone, no benefit of coinduction and comaintenance with midazolam and propofol could be demonstrated with respect to hemodynamic reactions and sympathoadrenergic and other endocrine stress response as well. Recovery was significantly delayed after administration of midazolam.

Aged↗
PubMed2002

The influence of preoperative chemotherapy and surgical technique in the treatment of hepatoblastoma--a report from the German Cooperative Liver Tumour Studies HB 89 and HB 94.

UNLABELLED: Despite the success of chemotherapy in the treatment of hepatoblastoma (HB), the complete surgical resection of the primary liver tumour and metastases is the most important factor for survival. METHODS: From 1989 to 1998, 141 children with HB were treated in the German Cooperative Paediatric Liver Tumour Study HB 89 and HB 94. The study determines the results of surgical strategy, which adapts the procedure at the initial operation to the tumour extension in the liver and the occurrence of metastases. RESULTS: The median follow-up of the survivors was 72 months (range 24 - 132 months). 98/141 (78 %) patients were alive and 31/141 (22 %) died. 12/141 (8.5 %) children had no surgical treatment. A complete resection of the primary tumour was achieved in 107/129 (83 %) cases. Forty-eight children were primary resected and eighty-one children were operated on after initial chemotherapy. In 36 cases, an atypical tumour resection, in 90 cases an anatomical liver resection, was performed. Three children were transplanted. There was no perioperative death. 14/48 (30 %) children with primary tumour resection had microscopical or macroscopical residual tumour in the liver. Despite the larger number of advanced HB in the primary chemotherapy group, an incomplete tumour resection was performed in only 15/78 (19 %) cases after liver resection (p < 0.044). 14/36 (38 %) cases with atypical tumour resection and only 16/90 (18 %) cases with anatomical liver resection had residual tumours in the liver (p < 0.019). These results underline the necessity for preoperative chemotherapy in all HB, which was accepted in the following study HB 99. Atypical tumour resection should be avoided because of the higher rate of incomplete tumour resections and local relapse compared to the group with anatomical tumour resection.

Adolescent↗
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↗