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Biomedical subjects

G Lenz

Publications and source records attributed to G Lenz.

At least 37 records · Page 2Linked to original sources

P(2Y) purinoceptor subtypes recruit different mek activators in astrocytes.

Extracellular ATP can function as a glial trophic factor as well as a neuronal transmitter. In astrocytes, mitogenic signalling by ATP is mediated by metabotropic P(2Y) receptors that are linked to the extracellular signal regulated protein kinase (Erk) cascade, but the types of P(2Y) receptors expressed in astrocytes have not been defined and it is not known whether all P(2Y) receptor subtypes are coupled to Erk by identical or distinct signalling pathways. We found that the P(2Y) receptor agonists ATP, ADP, UTP and 2-methylthioATP (2MeSATP) activated Erk and its upstream activator MAP/Erk kinase (Mek). cRaf-1, the first kinase in the Erk cascade, was activated by 2MeSATP, ADP and UTP but, surprisingly, cRaf-1 was not stimulated by ATP. Furthermore, ATP did not activate B-Raf, the major isoform of Raf in the brain, nor other Mek activators such as Mek kinase 1 (MekK1) and MekK2/3. Reverse transcriptase-polymerase chain reaction (RT - PCR) studies using primer pairs for cloned rat P(2Y) receptors revealed that rat cortical astrocytes express P(2Y(1)), a receptor subtype stimulated by ATP and ADP and their 2MeS analogues, as well as P(2Y(2)) and P(2Y(4)), subtypes in rats for which ATP and UTP are equipotent. Transcripts for P(2Y(6)), a pyrimidine-preferring receptor, were not detected. ATP did not increase cyclic AMP levels, suggesting that P(2Y(11)), an ATP-preferring receptor, is not expressed or is not linked to adenylyl cyclase in rat cortical astrocytes. These signal transduction and RT - PCR experiments reveal differences in the activation of cRaf-1 by P(2Y) receptor agonists that are inconsistent with properties of the P(2Y(1)), P(2Y(2)) and P(2Y(4)) receptors shown to be expressed in astrocytes, i.e. ATP=UTP; ATP=2MeSATP, ADP. This suggests that the properties of the native P(2Y) receptors coupled to the Erk cascade differ from the recombinant P(2Y) receptors or that astrocytes express novel purine-preferring and pyrimidine-preferring receptors coupled to the ERK cascade.

Adenosine Diphosphate↗

Time-dependent enhancement of inhibitory avoidance retention and MAPK activation by post-training infusion of nerve growth factor into CA1 region of hippocampus of adult rats.

Several studies have demonstrated that chronic intracerebroventricular nerve growth factor (NGF) infusion has a beneficial effect on cognitive performance of lesioned as well as old and developing animals. Here we investigate: (i) the effect of post-training infusion of NGF into the CA1 region of hippocampus on inhibitory avoidance (IA) retention in rats; (ii) the extension of the effect, in time and space, of NGF infusion into CA1 on the activity of mitogen-activated protein kinase (MAPK, syn: ERK1/2, p42/p44 MAPK). NGF was bilaterally injected into the CA1 regions of the dorsal hippocampus (0.05, 0.5 or 5.0 ng diluted in 0.5 microL of saline per side ) at 0, 120 or 360 min after IA training in rats. Retention testing was carried out 24 h after training. The injection of 5.0 and 0.5, but not 0.05, ng per side of NGF at 0 and 120 min after IA training enhanced IA retention. The highest dose used was ineffective when injected 360 min after training. The infusion of 0. 5 microL of NGF (5.0 ng) induced a significant enhancement of MAPK activity in hippocampal microslices; this enhancement was restricted to a volume with 0.8 mm radius at 30 min after injection. The MAPK activation was still seen 180 min after NGF infusion, although this value showed only a tendency. In conclusion, localized infusion of NGF into the CA1 region enhanced MAPK activity, restricted in time and space, and enhanced IA retention in a time- and dose-dependent manner.

Age Factors↗

[Psychopharmaceuticals and breast feeding].

The frequency of postnatal mental disorders requiring psychopharmacological treatment raises the question whether breast feeding can be recommended in some cases. This paper summarizes recent information regarding benefits and risks of breast feeding for infants of psychopharmacologically treated mothers. If a mother insists upon breast feeding, a careful risk-benefit-consideration has to take place. New results indicate that the advantages of breast feeding can outweight the given risks of maternal pharmacotherapy, if minimal necessary drug-doses of an agent with a small amount of passage into milk are prescribed. Monitoring of the serum-levels is advisable especially during the first three months. The nursing infant has to be closely controlled for any adverse effects.

Adult↗

Postoperative residual paralysis and respiratory status: a comparative study of pancuronium and vecuronium.

The objective of this prospective double-blind study was to determine whether postoperative residual paralysis (PORP) after pancuronium or vecuronium results in hypoxemia and hypercapnia in the immediate admission period to the recovery ward. Eighty-three consecutive surgical patients received balanced or intravenous anesthesia with pancuronium for operations lasting longer than one hour or vecuronium for those lasting less than 60 min, both combined with neostigmine at the end of anesthesia. Standard clinical criteria assessed neuromuscular function intraoperatively. Postoperatively, we determined neuromuscular function (acceleromyography with supramaximal train-of-four (TOF) stimulation of the ulnar nerve, and a 5-s head lift) and pulmonary function (pulse oximetry: SpO2, and blood gas analysis: SaO2, PaCO2). We defined PORP as a TOF-ratio <70%, hypoxemia as a postoperative SpO2 > or =5% below the pre-anesthestic level together with a postoperative SaO2 <93%, and hypercapnia as a PaCO2 > or =46 mm Hg. Among the 49 pancuronium and 27 vecuronium patients studied, the PORP rates were 20% in the pancuronium group and 7% in the vecuronium group (p>0.05). Hypoxemia and hypercapnia occurred more often in pancuronium patients with PORP than in those without PORP namely 60% vs. 10% (p<0.05) and 30% vs. 8% (p>0.05), respectively. We conclude that PORP after pancuronium is a significant risk factor for hypoxemia.

Double-Blind Method↗

Non-adherence with long-term prophylaxis: a 6-year naturalistic follow-up study of affectively ill patients.

In a retrospective 6-year follow-up, we assessed the reasons for and the frequency and consequences of non-adherence in 76 affectively ill patients receiving lithium prophylaxis in two lithium clinics. Thirty-eight bipolar (50%), 21 unipolar (27.6%) and 17 schizoaffective patients (22.4%) diagnosed according to DSM-III-R, were investigated with a specialized follow-up documentation. Of the patients 53.9% discontinued prophylaxis at some time; 43.2% of the discontinuations occurred during the first 6 months. In contrast to other studies the main reason reported for non-adherence was resistance against long-term treatment. According to the Lithium Attitudes Questionnaire non-adherent patients showed significantly less acceptance of the prophylaxis in general, of the effectiveness of lithium and of the severity of their illness than adherent patients. In a multivariate analysis of various parameters, only the negative attitude to prophylaxis correlated significantly with non-adherence. Significant correlation was found between treatment outcome and duration of initial prophylaxis. During the 6-year follow-up only the adherent patients showed a significant reduction of the number and duration of admissions. Our findings confirmed non-adherence as a major problem in the effectiveness of lithium prophylaxis. The authors recommend prospective investigations of attitudes and the impact of psychoeducation on long-term adherence.

Antimanic Agents↗

Dose-dependent impairment of inhibitory avoidance retention in rats by immediate post-training infusion of a mitogen-activated protein kinase kinase inhibitor into cortical structures.

Mitogen-activated protein kinase (MAPK) is a serine/threonine protein kinase abundantly expressed in postmitotic neurons of the developed nervous system. MAPK is activated in and required for both the induction of long-term potentiation (LTP) in hippocampal slices and the acquisition of fear conditioning training in rats. The present work was performed in order to test the effect of the specific inhibitor of MAPK kinase (MAPKK), PD 098059, on retention of a step-down inhibitory avoidance (IA). Adult male Wistar rats were bilaterally injected (0.5 microl/side) with PD 098059 (at 0.5, 5, or 50 microM) or vehicle into the entorhinal cortex or into the parietal cortex immediately after IA training using a 0.4 mA footshock. Retention testing was carried out 24 h after training. PD 098059 impaired retention when injected into the entorhinal cortex at the dose of 50 microM, but not at the doses of 5 or 0.5 microM. When infused into the parietal cortex, PD 098059 was amnestic at the doses of 5 and 50 microM. The drug had no effect when infused at the highest dose in either structure 6 h after training. Our results suggest that the MAPKK inhibitor impairs IA retention memory in a dose-dependent manner when injected immediately after training into entorhinal cortex or parietal cortex. The effective dose is variable according to the neocortical structure studied.

Animals↗

Frequent expression of the B-cell-specific activator protein in Reed-Sternberg cells of classical Hodgkin's disease provides further evidence for its B-cell origin.

The neoplastic cells of classical Hodgkin's disease (cHD), ie, Hodgkin and Reed-Sternberg cells (HRS cells), contain clonally rearranged Ig genes, but are dissimilar to normal B cells in that they mostly do not display B-cell antigens such as CD20 or CD19. The transcription factor B-cell-specific activator protein (BSAP) influences numerous B-cell functions such as B-cell antigen expression, Ig expression, and class switch. We analyzed the expression of BSAP in cHD and control tissues by isotopic in situ hybridization and immunohistochemistry to determine whether BSAP is expressed in HRS cells and, if so, whether it may be involved in the genesis of the abnormal phenotype of these cells. Both in normal lymphoid tissue and non-Hodgkin lymphomas, BSAP transcripts and protein were almost exclusively found in B cells and B-cell lymphomas (40 cases), but were absent from the tumor cells of T-cell neoplasms (41 cases), including 19 cases of anaplastic large cell lymphoma of T- and null-cell type. Among cHD, variable numbers of HRS cells exhibited BSAP transcripts (22 of 25 cases) and protein (28 of 31 cases). Our findings show that BSAP is sufficiently specific to serve as B-cell marker. BSAP expression in HRS cells provides further strong evidence for a frequent B-cell origin of cHD and helps distinguish this disease from anaplastic large cell lymphoma of T- and null-cell type. Because BSAP is much more frequently expressed in HRS cells than the conventional B-cell antigens, the abnormal immunophenotype of HRS cells with frequent absence of B-cell antigens does not appear to be due to absent BSAP expression.

B-Lymphocytes↗

Neurological complaints after unsuccessful spinal anaesthesia as a manifestation of incipient syringomyelia.

The medical literature sometimes reports neurological complications after spinal or epidural anaesthesia. In a few cases, the onset of symptoms can be a sign of a pre-existing disease without a primary connection with regional anaesthesia. In the following case report, the patient complained of paraesthesias in both legs after a failed spinal anaesthesia, even though the needle had been placed intrathecally. Only neurological examination and nuclear magnetic resonance imaging revealed the presence of syringomyelia.

Aged↗

Stereoselective differences in the vasorelaxing effects of S(+) and R(-) ketamine on rat isolated aorta.

BACKGROUND: S(+) ketamine, because of its higher anesthetic potency and lower risk of psychotomimetic reactions, has been suggested to be superior to presently available racemic ketamine. The racemate is a direct vasodilator in vivo, and thus the authors investigated the vasorelaxing effects of ketamine enantiomers on rat aorta. METHODS: Rat isolated aortic rings with and without endothelium were contracted with 3 x 10(-7) M norepinephrine. Then 10(-5) to 3 x 10(-3) M S(+), R(-), or racemic ketamine were added cumulatively. Vascular responses to ketamine were further studied in rings pretreated with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (NNLA), the adenosine triphosphate-sensitive K+ channel antagonist glibenclamide, and the L-type calcium channel blocking agent D888. RESULTS: Ketamine enantiomers and the racemate produced concentration-dependent vasorelaxation. The relaxing effect of S(+) ketamine was significantly weaker compared with R(-) ketamine and the racemate reflected by the half-maximum effective concentration (EC50) values of 11.6 x 10(-4), 4.8 x 10(-4), and 6 x 10(-4) M, respectively. Removal of the endothelium and NNLA or glibenclamide pretreatment did not significantly alter the vasorelaxing effect of ketamine. In contrast, D888 pretreatment significantly shifted the concentration-effect curves of both S(+) and R(-) ketamine rightward (EC50 values of 18.9 x 10(-4) and 8.5 x 10(-4) M, respectively), whereas the difference between the isomers was not affected. CONCLUSIONS: Vasorelaxation by ketamine enantiomers is quantitatively stereoselective: The effect of S(+)ketamine is significantly weaker compared with that of the racemate and R(-) ketamine. This stereoselective difference is not due to nitric oxide release, activation of adenosine triphosphate-sensitive potassium channels, or differential inhibition of L-type calcium channels.

Anesthetics, Dissociative↗

Intraoperative magnetic resonance imaging with the magnetom open scanner: concepts, neurosurgical indications, and procedures: a preliminary report.

OBJECTIVE: Intraoperative magnetic resonance imaging (MRI) is now available with the General Electric MRI system for dedicated intraoperative use. Alternatively, non-dedicated MRI systems require fewer specific adaptations of instrumentation and surgical techniques. In this report, clinical experiences with such a system are presented. METHODS: All patients were surgically treated in a "twin operating theater," consisting of a conventional operating theater with complete neuronavigation equipment (StealthStation and MKM), which allowed surgery with magnetically incompatible instruments, conventional instrumentation and operating microscope, and a radiofrequency-shielded operating room designed for use with an intraoperative MRI scanner (Magnetom Open; Siemens AG, Erlangen, Germany). The Magnetom Open is a 0.2-T MRI scanner with a resistive magnet and specific adaptations that are necessary to integrate the scanner into the surgical environment. The operating theaters lie close together, and patients can be intraoperatively transported from one room to the other. This retrospective analysis includes 55 patients with cerebral lesions, all of whom were surgically treated between March 1996 and September 1997. RESULTS: Thirty-one patients with supratentorial tumors were surgically treated (with navigational guidance) in the conventional operating room, with intraoperative MRI for resection control. For 5 of these 31 patients, intraoperative resection control revealed significant tumor remnants, which led to further tumor resection guided by the information provided by intraoperative MRI. Intraoperative MRI resection control was performed in 18 transsphenoidal operations. In cases with suspected tumor remnants, the surgeon reexplored the sellar region; additional tumor tissue was removed in three of five cases. Follow-up scans were obtained for all patients 1 week and 2 to 3 months after surgery. For 14 of the 18 patients, the images obtained intraoperatively were comparable to those obtained after 2 to 3 months. Intraoperative MRI was also used for six patients undergoing temporal lobe resections for treatment of pharmacoresistant seizures. For these patients, the extent of neocortical and mesial resection was tailored to fit the preoperative findings of morphological and electrophysiological alterations, as well as intraoperative electrocorticographic findings. CONCLUSION: Intraoperative MRI with the Magnetom Open provides considerable additional information to optimize resection during surgical treatment of supratentorial tumors, pituitary adenomas, and epilepsy. The twin operating theater is a true alternative to a dedicated MRI system. Additional efforts are necessary to improve patient transportation time and instrument guidance within the scanner.

Adolescent↗

Dynamic tracking in interventional MRI using wavelet-encoded gradient-echo sequences.

This work describes a newly developed magnetic resonance imaging (MRI) data-acquisition strategy which replaces the standard Fourier phase-encoding with the spatially localized coefficients of wavelet-encoding and offers a new technique for image guidance when combined with a dynamic tracking algorithm. By using this new technique, only a specific fraction of the entire raw data set needs to be updated and reconstructed to visualize the movement of an interventional device during an MR guided procedure. The combination of wavelet-encoding and a dynamic tracking algorithm was implemented in two-dimensional and three-dimensional gradient-echo sequences on a 0.2-T open C-arm-shaped MR system (Siemens, Erlangen Germany) and tested in phantom and in vitro experiments. When applying the wavelet-encoding direction parallel to the movement of a straight interventional device, only those spatially localized wavelet-coefficients mainly affected by the interventional device are updated. This led to potential increases of the image frame rate by a factor of up to seven.

Animals↗

Interactive MR imaging-guided biopsy and aspiration with a modified clinical C-arm system.

OBJECTIVE: This investigation was performed to test the hypotheses that interactive guidance of MR image acquisition during needle-directed procedures using a clinical 0.2-T C-arm open MR imaging system integrated with a frameless optically linked stereotaxy system is feasible, and that procedure times can be sufficiently short to be well tolerated by the patient. SUBJECTS AND METHODS: One hundred six MR-guided procedures were performed in 86 patients (ranging in age from 5 months to 88 years) using a clinical C-arm imaging system supplemented with an in-room RF-shielded liquid crystal display monitor, a frameless stereotaxy system, rapid gradient-echo sequences for needle guidance, and MR-compatible monitoring and surgical lighting equipment. We performed 50 biopsies and aspirations of the head and neck in 37 patients, 23 biopsies of musculoskeletal lesions in 22 patients, 16 biopsies of abdominal sites in 10 patients, six biopsies of the thoracolumbar spine or sacrum in six patients, and 11 shoulder joint injections for MR arthrography in 11 patients, in addition to 38 MR arthrographic injections on the same imaging system described in a previous report. Tissue sampling included fine-needle aspiration (n = 90) and cutting needle core biopsy (n = 41). Thirty-five patients underwent both procedures. Procedures were evaluated for success of needle placement, procedure time, and complications. RESULTS: Needle placement was successful in all cases, and no complications occurred. Tissue was sufficient for pathologic diagnosis for all but eight patients. Passes per patient averaged 2.1. For fine-needle aspiration, instrument time averaged 7 min 42 sec per pass, cutting needle core biopsy averaged 6 min 24 sec, and shoulder injection averaged 8 min. CONCLUSION: MR imaging guidance for needle procedures on a clinical 0.2-T C-arm system with supplemental interventional accessories is feasible, with relatively rapid needle placement.

Abdomen↗

[Psychotropic drugs in pregnancy: uses and risks].

To reduce insecurities concerning the pros and cons of psychopharmacological treatment of mental disorders during pregnancy, recent papers on teratogenic risks of different (groups of) drugs, and on therapeutic strategies of psychiatry disorders were reviewed and the results summarised. Psychotropic medication sometimes increases the risk of congenital malformations. It may cause peripartal toxicity and neurobehavioral changes; on the other hand, these risks have to be weighted against the proven benefits of the drugs. Untreated mental disorders seriously endanger the offspring during pregnancy and after delivery, and hence psychopharmacological treatment may be advisable in spite of the risks involved.

Abnormalities, Drug-Induced↗

Temporal profiles of the in vitro phosphorylation rate and immunocontent of glial fibrillary acidic protein (GFAP) after kainic acid-induced lesions in area CA1 of the rat hippocampus: demonstration of a novel phosphoprotein associated with gliosis.

The in vitro phosphorylation rate and immunocontent of glial fibrillary acidic protein was studied in slices of area CA1 of the rat hippocampus after stereotaxic injection of 1 nmol of kainic acid. For controls the contralateral hippocampus was injected with saline. Hippocampal tissue was incubated with [32P]phosphate and analysed by two-dimensional electrophoresis for phosphorylation rate and by immunoblotting for immunocontent. Both these parameters decreased during the first 4 days after injection and then started to increase at 10 days and continued to increase until at least 84 days. Except for a small excess of phosphorylation rate at 28 days, the relationship between immunocontent and in vitro phosphorylation rate of glial fibrillary acidic protein remained constant, indicating that the reactive gliosis was not associated with hypo- or a major hyperphosphorylation of this protein. Histology showed a pronounced loss of CA1 pyramidal cells 1 day after injection. At 28 days after injection the pyramidal cells had disappeared and only a few abnormal neurones were present. In contrast, immunocytochemistry after 28 days showed a marked increase in astrocytes reacting positive to the antibody in the strata radiatum and lacunosum moleculare. Besides glial fibrillary acidic protein the expression of several other proteins was upregulated as a result of the injection of kainic acid. These included phosphovimentin and an unknown phosphoprotein designated pp25 which co-migrated on 2-D gels with a prominent phosphoprotein expressed in primary cultures of astrocytes. Pp25 was expressed in lesioned tissue more frequently than phosphovimentin and with a time course that started earlier. Of particular interest was the expression of pp25 in the contralateral saline-injected hippocampus 1 day after injection of kainic acid. It is possible that pp25 will prove to be a sensitive marker of gliosis.

Animals↗

Intraoperative diagnostic and interventional magnetic resonance imaging in neurosurgery.

OBJECTIVE: The benefits of intraoperative magnetic resonance (MR) imaging for diagnostic and therapeutic measures are as follows: 1) intraoperative update of data sets for navigational systems, 2) intraoperative resection control of brain tumors, and 3) frameless and frame-based on-line MR-guided interventions. The concept of an intraoperative MR scanner in the sterile environment of operating theater is presented, and its advantages, disadvantages, and limitations are discussed. METHODS: A 0.2-tesla magnet (Magnetom Open; Siemens AG, Erlangen, Germany) inside a radiofrequency cabin with a radiofrequency-shielded sliding door was installed adjacent to one of the operating theaters. A specially designed patient transport system carried the patient in a fixed position on an air cushion to the scanner and back to the surgeon. RESULTS: In a series of 27 patients, intraoperative resection control was performed in 13 cases, with intraoperative reregistration in 4 cases. Biopsies, cyst aspirations, and catheter placements (mainly frameless) were performed under direct MR visualization with fast image sequences. The MR-compatible equipment and the patient transport system are safe and reliable. CONCLUSION: Intraoperative MR imaging is a safe and successful tool for surgical resection control and is clearly superior to computed tomography. Intraoperative acquisition of data sets eliminates the problem of brain shift in conventional navigational systems. Finally, on-line MR-guided interventional procedures can be performed easily with this setting. As with all MR systems, individual testing with phantoms, application of correction programs, and determination of the optimal amount of contrast media are absolute prerequisites to guarantee patient safety and surgical success.

Adult↗