Biomedical subjects

Michael Zimmermann

Publications and source records attributed to Michael Zimmermann.

28 records · Page 2Linked to original sources

PubMed2003

Serum S-100B protein as a molecular marker in severe traumatic brain injury.

PURPOSE: There is growing evidence that S-100B protein may be used as a novel biochemical marker of brain cell damage, measured by a simple blood test. In this paper, we summarize the current knowledge about S-100B serum measurements in severe head injury and address actual controversies. METHODS: The material of the present analysis consists of a MEDLINE literature search for S-100 and severe head injury from 1966 to 2003. Studies of S-100B in severe head injury were reviewed for their information about the potential clinical value of this marker. RESULTS: A total of 18 clinical studies were identified and reviewed. Peak values of serum S-100B were demonstrated to have the highest correlation to any endpoint parameter. Admission values also have a significant correlation to injury severity and outcome but show a highly time dependent temporal course. There is extracranial release of S-100B in multitrauma patients in the first 48 hours, but the impact is limited as many studies have found a clear relationship between S-100B and injury severity, imaging findings and outcome. CONCLUSION: S-100B belongs to a new generation of molecular serum markers of brain damage. These markers will have potential as a surrogate outcome marker or monitoring parameters for both clinical and experimental settings.

Biomarkers↗

PubMed2002

[D-Val22]big ET-1[16-38] inhibits endothelin-converting enzyme activity: a promising concept in the prevention of cerebral vasospasm.

The aim of this study was to investigate whether the blocking of endothelin-converting enzyme (ECE) activity offers a new approach to inhibiting the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) by preventing transformation of big endothelin-1 (big ET-1) to vasoactive endothelin-1 (ET-1). The effect of potential ECE inhibitors was determined in vitro by measurement of isometric contractions, induced by big ET-1, in isolated rat basilar arteries. Intact and de-endothelialized endothelium (E+ and E-, respectively) segments were examined after preincubation with the putative ECE inhibitors: phosphoramidon (10(-4) M), and [22D-Val]big ET-1 [16-38] (10(-5) M and 10(-6) M). Additionally, the effect of [D-Val22]big ET-1 [16-38] was investigated in rabbits after intracisternal application in order to inhibit the contraction of the basilar artery induced by (2x10(-6) M) big ET-1. Application of 10(-4)-M phosphoramidon resulted in a statistically significant decrease in big ET-1-induced contraction in E+ and E- segments; 10(-5)-M and 10(-6)-M [22D-Val]big ET-1 [16-38] in E- segments produced no statistically significant effect. The application of 10(-6)-M [22D-Val]big ET-1 [16-38] in E+ segments caused increased contractions, as shown by the shift to the left of the concentration-effect curve (CEC). In the rabbit group pretreated with [D-Val22]big ET-1 [16-38] (2x10(-5) M) (n=8), the angiographically measured diameter of the basilar artery increased from 0.63+/-0.12 mm to 0.66+/-0.12 mm. In the control group (n=8), this diameter decreased from 0.71+/-0.13 mm to 0.57+/-0.15 mm. This corresponded to an increase in vessel diameter of 5.24+/-9.89% in the treatment group and a decrease of 19.54+/-15.81% in the control group (P=0.002). The present study indicates the existence of functional ECE activity in rat basilar artery, which differs in the endothelium and the smooth muscle layer. These results demonstrate that [D-Val22]big ET-1 [16-38] has a potent ECE-inhibitory effect, preventing cerebral vasospasm in rabbit basilar artery by inhibiting the transformation of big ET-1 to vasoactive ET-1 after intracisternal application in vivo, whereas no inhibitory effect was detectable in rat basilar artery in vitro. Therefore, further studies of the biochemical nature of cerebrovascular ECE activity are required.

Animals↗

PubMed2002

Effect of the novel endothelin(A) receptor antagonist LU 208075 on contraction and relaxation of isolated rat basilar artery.

Increased levels of endothelin (ET)-1 and bigET-1 may be responsible for enhanced cerebroarterial resistance under pathologic conditions. Therefore, the effect of LU 208075, a novel ET(A)-selective receptor antagonist was determined. The aim of the study was to investigate in vitro the inhibitory effect of LU 208075 on ET-1 and bigET-1 induced contraction and relaxation in rat basilar artery segments. Segments with (E+) and without (E-) endothelium were prepared for the measurement of isometric force. Concentration-effect curves (CECs) were constructed by cumulative application of ET-1 or bigET-1. The shift of the CECs in the presence of LU 208075 against the control curve was determined. Relaxation was investigated on precontracted segments, calculated in percentage decrease of precontraction and compared by the pD(2) and E(max). ET-1 and bigET-1 induced contraction was dose dependently inhibited by LU 208075. Shifts of the CECs in the presence of LU 208075 (10(-6) M and 10(-5) M) were for ET-1 (1) in E+: 4.4 and 19.7; (2) in E-: 8.1 and 60.4 and for bigET-1 (3) in E+: 10.8 and (4) in E-: 26.0 respectively. LU 208075 (10(-5) M) completely inhibited bigET-1-induced contraction. Relaxation by ET-1 or bigE-1 was only observed in the presence of LU 208075. CECs were shifted to the right by LU 208075 (10(-5) M) by a factor of 24 (ET-1) and 4.5 (bigET-1). E(max) values were 45+/-18% and 51+/-15% (ET-1; in the presence of 10(-5) and 10(-6) M LU 208075 respectively), and 56+/-20% and 49+/-17% (bigET-1; in the presence of 10(-5) and 10(-6) M LU 208075 respectively). The data suggests a competitive ET(A)-receptor inhibition by LU 208075. The enhanced inhibitory effect on bigET-1-induced contraction could indicate an additional inhibitory effect on endothelin-converting enzyme activity. The pronounced effect on E-vessels and the inhibition of relaxation may suggest an ET(B) receptor affinity.

Animals↗

PubMed2002

Does the A118G polymorphism at the mu-opioid receptor gene protect against morphine-6-glucuronide toxicity?

BACKGROUND: Some, but not all, patients with renal dysfunction suffer from side effects after morphine administration because of accumulation of the active metabolite morphine-6-glucuronide (M6G). The current study aims to identify genetic causes that put patients at risk for, or protect them from, opioid side effects related to high plasma M6G. Candidate genetic causes are the single nucleotide polymorphism (SNP) A118G of the mu-opioid-receptor gene (OPRM1), which has recently been identified to result in decreased potency of M6G, and mutations in the MDR1-gene coding P-glycoprotein, of which morphine and M6G might be a substrate. METHODS: Two men, aged 87 and 65 yr, with renal failure (creatinine clearance of 6 and 9 ml/min) received 30 mg/day oral morphine for pain treatment. Both patients had sufficient analgesia from morphine. However, while one patient tolerated morphine well despite high plasma M6G of 1735 nM, in the patient with M6G plasma concentrations of 941 nM it caused severe sleepiness and drowsiness. Patients were genotyped for known SNPs of the OPRM1 and MDR1 genes. RESULTS: The patient who tolerated morphine well despite high plasma M6G was a homozygous carrier of the mutated G118 allele of the mu-opioid-receptor gene, which has been previously related to decreased M6G potency. In contrast, the patient who suffered from side effects was "wild-type" for this mutation. No other differences were found between the OPRM1 and MDR1 genes. CONCLUSIONS: The authors hypothesize that the A118G single nucleotide polymorphism of the mu-opioid-receptor is among the protective factors against M6G-related opioid toxicity. The observation encourages the search for pharmacogenetic reasons that cause interindividual variability of the clinical effects of morphine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Laser surface scanning for patient registration in intracranial image-guided surgery.

OBJECTIVE: To report our clinical experience with a new laser scanning-based technique of surface registration. We performed a prospective study to measure the calculated registration error and the application accuracy of laser surface registration for intracranial image-guided surgery in the clinical setting. METHODS: Thirty-four consecutive patients with different intracranial diseases were scheduled for intracranial image-guided surgery by use of a passive infrared surgical navigation system. Surface registration was performed by use of a Class I laser device that emits a visible laser beam. The Polaris camera system (Northern Digital, Waterloo, ON, Canada) detects the skin reflections of the laser, which the software uses to generate a virtual three-dimensional matrix of the anatomy of each patient. An advanced surface-matching algorithm then matches this virtual three-dimensional matrix to the three-dimensional magnetic resonance therapy data set. Registration error as calculated by the computer was noted. Application accuracy was assessed by use of the localization error for three distant anatomic landmarks. RESULTS: Laser surface registration was successful in all patients. For the surgical field, application accuracy was 2.4 +/- 1.7 mm (range, 1-9 mm). Application accuracy was higher for the surgical field of frontally located lesions (mean, 1.8 +/- 0.8 mm; n = 13) as compared with temporal, parietal, occipital, and infratentorial lesions (mean, 2.8 +/- 2.1 mm; n = 21). CONCLUSION: Laser scanning for surface registration is an accurate, robust, and easy-to-use method of patient registration for image-guided surgery.

Adolescent↗

PubMed2002

Effect of intraventricular sodium nitroprusside on cerebral hemodynamics and oxygenation in poor-grade aneurysm patients with severe, medically refractory vasospasm.

OBJECTIVE: Sodium nitroprusside (SNP) was recently suggested as a treatment for cerebral ischemia in patients with severe, medically refractory vasospasm after subarachnoid hemorrhage. In this study, we sought to objectify the effect on cerebral hemodynamics and oxygenation (PbrO2) when using intraventricular SNP as a last resort therapy in poor-grade patients with subarachnoid hemorrhage; severe, medically refractory vasospasm; and compromised cerebral blood flow. METHODS: Thirteen of 185 consecutive patients with subarachnoid hemorrhage developed severe, medically refractory vasospasm and were treated with intraventricular SNP. All of these patients' neurological conditions were classified as Hunt and Hess Grade IV. SNP doses ranged from 10 to 40 mg with single-dose treatment and from 2 to 8 mg/h with continuous infusion. Angiography or PbrO2 measurement was used to assess the treatment effects. RESULTS: In 6 of the 13 patients, SNP improved cerebral hemodynamics, as demonstrated by increased PbrO2 or decreased cerebral circulation time. Only 1 patient showed increased diameter of the spastic vessel, however. Maximum increase in PbrO2 ranged from 5 to 52 mmHg. Adverse effects were hypertension in five patients, vomiting in three patients, and cardiac arrhythmia in one patient. Cerebral infarctions caused by vasospasm occurred in 6 (46%) of the 13 patients. No differences between SNP responders and SNP nonresponders were noted. CONCLUSION: In patients with severe, medically refractory vasospasm, intraventricular SNP may improve PbrO2 and cerebral blood flow, but the effect is highly variable. On the basis of the improvements we observed in 6 of 13 patients, intraventricular SNP administration is justified as a last resort therapy in patients with cerebral ischemia and impending infarction. Our findings suggest that SNP may be more effective when initiated early and administered continuously.

Adult↗

PubMed2002

Increased risk for postoperative hemorrhage after intracranial surgery in patients with decreased factor XIII activity: implications of a prospective study.

BACKGROUND AND PURPOSE: The functional integrity of the hemostatic system is a prerequisite for the safe performance of neurosurgical procedures. To monitor the individual coagulation capacity of each patient, standard tests are effective to detect deficiencies involving the generation of fibrin. However, fibrin clot strength depends primarily on coagulation factor XIII, which cross-links fibrin monomers and enhances clot resistance against fibrinolysis. Therefore, factor XIII is functionally involved in both the hemostatic and fibrinolytic systems. The objective of this prospective study was to determine the incidence and clinical relevance of perioperative decreased factor XIII with respect to standard coagulation parameters and the occurrence of postoperative hematoma. METHODS: In 876 patients, 910 neurosurgical procedures were performed. Prothrombin time (PT), partial thromboplastin time (PTT), platelet count, fibrinogen, and factor XIII were tested in each patient preoperatively and postoperatively. RESULTS: Postoperative intracranial hematoma (defined as requiring surgical evacuation) occurred after 39 (4.3%) of 910 surgical procedures. Patients with postoperative hematoma had significantly lower factor XIII and fibrinogen levels preoperatively and postoperatively than patients without hematoma. In patients with postoperative hematoma, PT and platelets differed significantly only postoperatively, whereas PTT was different neither preoperatively nor postoperatively. Of the 39 patients with a postoperative hematoma, 13 (33.3%) had a postoperative factor XIII <60% compared with 61 (7%) of 867 patients without hematoma (P<0.01, Fisher's exact test). The relative risk of developing a postoperative hematoma is therefore increased 6.4-fold in patients with postoperative factor XIII <60%. The risk is increased 12-fold in patients who additionally have postoperative decreased fibrinogen levels (<1.5 g/L) and 9-fold in patients with platelet count <150x10(9)/L and factor XIII <60%. CONCLUSIONS: This is the first prospective study that demonstrates the association of decreased perioperative factor XIII with an increased risk of postoperative hematoma in neurosurgical patients. The risk is further increased in those patients with low factor XIII and additional abnormalities of fibrinogen, PT, platelets, and PTT. Factor XIII testing and specific replacement, as accepted for other clotting factors, may reduce the risk of postoperative hematoma.

Comorbidity↗

PubMed2002

Endothelin-converting enzyme activity in human cerebral circulation.

OBJECTIVE: An increased level of endothelin (ET)-1 seems to be involved in the development of augmented cerebrovascular resistance in different pathological conditions, most notably vasospasm after subarachnoid hemorrhage. Therefore, interfering with the ET synthesis or ET receptor blockade may be a promising approach in the treatment of cerebral vasospasm after subarachnoid hemorrhage. Although the receptors mediating the effects of ET-1 human cerebrovasculature are well characterized, data concerning the functionally relevant ET-converting enzyme (ECE) activity are scarce. METHODS: ECE activity was determined in organ bath studies by the use of intraoperatively harvested human pial arteries. The level of ECE activity was analyzed by comparing the shift in the concentration effect curves obtained for ET-1 and its precursor, big ET-1. In addition, the presence of ECE-1alpha immunoreactivity was studied in human cerebral tissue. RESULTS: ECE-1alpha immunoreactivity was found, although not consistently, in human cerebral arteries and was restricted to the endothelium. In isolated pial arterial segments, ET-1 and big ET-1 induced concentration-related contractions with mean pD(2) values of 9.25 +/- 0.34 and 7.13 +/- 0.17, respectively, yielding a 123-fold shift of big ET-1 versus mature ET-1. Preincubation with phosphoramidon (10(-4) mol/L) resulted in a small yet significant inhibition of the contraction induced by big ET-1. CONCLUSION: The results of our study indicate the presence of functional ECE activity and ECE-1alpha immunoreactivity in human cerebral arteries. Furthermore, the data suggest the presence of ECE-like activity that differs from that of ECE-1alpha.

Adult↗

PubMed2002

Robot-assisted navigated neuroendoscopy.

OBJECTIVE: Major steps in the evolution of advanced neurosurgical techniques include microneurosurgery, neuroendoscopy and its minimally invasive variations, neuronavigation, and advanced intraoperative imaging. With traditional neuroendoscopic techniques (e.g., freehand endoscopy or the use of mechanical arms), definitive controlled movement of the endoscope within the brain depends on the experience and skill of the individual neurosurgeon. METHODS: With the Evolution 1 precision robot (Universal Robot Systems, Schwerin, Germany), a new neurosurgical tool has become available for the precise steering of instruments within the cranium. After preclinical anatomic and precision studies, the system was used for neuronavigated endoscopic procedures for three patients. RESULTS: All robot-assisted, navigated, endoscopic procedures were successfully completed. The time for the registration procedure and setup of the robot decreased from 60 minutes for the first patient to 30 minutes for the third patient. The time for the surgical part of the endoscopic procedure ranged from 17 to 65 minutes. No complications occurred during any procedure. CONCLUSION: The use of robotic technology for neuroendoscopic procedures is a major advance for controlled movement of the endoscope within the cranium. The start-up procedure and calibration of the robot are still time-consuming, but the actual operation time is comparable to that of freehand neuroendoscopic procedures. Steering of the endoscope is facilitated, and the precision of the endoscopic movements is noteworthy.

Adolescent↗

PubMedDate not supplied

Cerebrovascular characterization of the novel nonpeptide endothelin-A receptor antagonist LU 208075.

Enhanced cerebrovascular resistance under pathologic conditions, like cerebral vasospasm after subarachnoid hemorrhage, seems to be caused by the vasocontractile effect of endothelin-1 (ET-1). Therefore, the effect of the novel and ET(A) receptor selective antagonist LU 208075 was characterized by the contraction and relaxation induced by ET-1 and bigET-1 on rat basilar artery. Basilar artery ring segments with (E+) and without (E-) functionally intact endothelium were prepared to measure the isometric force. Concentration-effect curves were constructed by cumulative application of ET-1 or bigET-1 in the presence of LU 208075 (10(-7)M, 10(-6)M, and 10(-5)M). The effect of LU 208075 was determined by the pA(2) value. The contraction by ET-1 and bigET-1 was inhibited by LU 208075 in a dose-dependent manner. The pA(2) values for ET-1 and for bigET-1 were 6.51 +/- 0.39 (E+) and 6.67 +/- 0.43 (E-), and 7.03 +/- 0.32 (E+) and 7.24 +/- 0.31 (E-) respectively. The E(max) values for bigET-1 but not for ET-1 were reduced significantly in the presence of LU 208075. A significant relaxation by ET-1 or bigET-1 was observed only in the presence of LU 208075. This relaxation was inhibited by LU 208075 in higher concentrations, with pA(2) values of 5.68 +/- 0.05 (ET-1) and 5.50 +/- 0.39 (bigET-1). The current data correlate with a competitive inhibition of ET(A) receptor-mediated contraction and relaxation, caused by ET(B) receptor activation on cerebral vessels by LU 208075. The selectivity for the ET(A) receptor was approximately sevenfold. Furthermore, the results may suggest an inhibition of the functional ET-converting enzyme activity by LU 208075.

Animals↗