Turning points: puntos de inflexión en la vida de los estudiantes de medicina / Turning points: moments of inflection in the lives of medical students

El objetivo del presente trabajo es contribuir con un acercamiento inicial al estudio de los turning points en cuanto temática relevante en la formación de los estudiantes de medicina. Hasta ahora los turning points se han estudiado poco dentro del campo de la educación médica. Se trata de un concepto que pone el acento en una variedad de situaciones y experiencias que tienen impacto significativo en las trayectorias vitales de los estudiantes, pero que no son fácilmente visibles. Los turning points son eventos que cambian la vida de los estudiantes. Sin embargo, muchas veces pasan desapercibidos y sólo se reconocen sus efectos años después del paso por la facultad. En esta colaboración se intenta una aproximación a su delimitación conceptual y a los mecanismos o metodología para identificarlos. De esta forma, surgen nuevos desafíos para el campo de la educación médica tanto desde la captación y la comprensión de un fenómeno difícil de identificar como desde las exigencias que implican su reconocimiento y promoción en el interior de las facultades de Ciencias de la Salud.(AU)

The aim of this paper is to contribute with an initial approach to the study of turning points in medical students training. Until now, there has been few research regarding turning points in the field of medical education. This concept highlights a variety of events and experiences that have a significant impact in life paths. Turning points in education are not easily visible, they often go unnoticed and they are only recognized years after graduation. It is relevant to study turning points in student's life paths in the field of medical education, both in terms of capturing and understanding a phenomenon that is difficult to identify, as well as from the demands that imply its recognition and promotion within the medical school.(AU)

Long-term effect of computer-assisted decision support for antibiotic treatment in critically ill patients: a prospective 'before/after' cohort study.

OBJECTIVES: Antibiotic resistance has risen dramatically over the past years. For individual patients, adequate initial antibiotic therapy is essential for clinical outcome. Computer-assisted decision support systems (CDSSs) are advocated to support implementation of rational anti-infective treatment strategies based on guidelines. The aim of this study was to evaluate long-term effects after implementation of a CDSS. DESIGN: This prospective 'before/after' cohort study was conducted over four observation periods within 5 years. One preinterventional period (pre) was compared with three postinterventional periods: directly after intensive implementation efforts (post1), 2 years (post2) and 3 years (post3) after implementation. SETTING: Five anaesthesiological-managed intensive care units (ICU) (one cardiosurgical, one neurosurgical, two interdisciplinary and one intermediate care) at a university hospital. PARTICIPANTS: Adult patients with an ICU stay of >48 h were included in the analysis. 1316 patients were included in the analysis for a total of 12,965 ICU days. INTERVENTION: Implementation of a CDSS. OUTCOME MEASURES: The primary end point was percentage of days with guideline adherence during ICU treatment. Secondary end points were antibiotic-free days and all-cause mortality compared for patients with low versus high guideline adherence. MAIN RESULTS: Adherence to guidelines increased from 61% prior to implementation to 92% in post1, decreased in post2 to 76% and remained significantly higher compared with baseline in post3, with 71% (p=0.178). Additionally, antibiotic-free days increased over study periods. At all time periods, mortality for patients with low guideline adherence was higher with 12.3% versus 8% (p=0.014) and an adjusted OR of 1.56 (95% CI 1.05 to 2.31). CONCLUSIONS: Implementation of computerised regional adapted guidelines for antibiotic therapy is paralleled with improved adherence. Even without further measures, adherence stayed high for a longer period and was paralleled by reduced antibiotic exposure. Improved guideline adherence was associated with reduced ICU mortality. TRIAL REGISTRATION NUMBER: ISRCTN54598675.

[Management of peripheral vascular disease based on current guidelines. Peripheral artery occlusive disease of the iliac and femoral arteries and carotid artery stenosis]. / Management peripherer Gefäßerkrankungen gemäß aktueller Leitlinien. Periphere arterielle Verschlusskrankheit vom Becken-Bein-Typ und extrakranielle Karotisstenose.

The article summarizes the recommendations of current European and American guidelines concerning the diagnosis and treatment of peripheral arterial occlusive disease and carotid artery stenosis. In comparison to older recommendations, current guidelines concerning endovascular treatment and concomitant medical therapy have been changed in recent years. With the exception of very complex and long lesions, endovascular methods are seen as the therapy of choice for revascularization of the iliac and femoral arteries. For cardiovascular risk reduction, patients with symptomatic peripheral arterial disease and stenosis of the carotid arteries should receive antiplatelet as well as statin therapy and should not be treated different from patients with coronary artery disease.

FR167653 Ameliorates expression of proinflammatory mediators in human umbilical venous endothelial cells and human monocytes.

p38MAP kinase plays a crucial role in intracellular signal transduction of inflammation. The inhibitor of p38 MAP kinase, FR167653, has been proven to be effective to suppress proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in various animal models. The aim of our study was to investigate p38MAP kinase inhibition by FR167653 on the inflammatory profile of cells involved in vascular injury. HUVEC incubated with FR167653 in concentrations of 0.1 to 20 mumol for 24 hours were stimulated with TNF-alpha (20 ng/mL). Human monocytes were incubated with equal concentrations of FR167653 and stimulated with lipopolysaccharides (LPS; 10 microg/mL). In monocytes, p38 MAP kinase could be inhibited by FR167653 (Western blot). The cytokines IL-6 and IL-8 were dose dependently downregulated by FR167653 (enzyme-linked immunosorbent assay) [ELISA]. These results were confirmed at a transcriptional level by real-time polymerase chain reaction (PCR). Gene expression of IL-6 and IL-8 was dose dependently downregulated. The expression pattern of ICAM-1 and VCAM-1 was not altered by FR167653 (ELISA). In HUVEC, the cytokines IL-6 and IL-8 were dose dependently downregulated by FR167653 (ELISA). These results were confirmed on a transcriptional level by real-time PCR. Gene expression of IL-6 and IL-8 were also dose dependently suppressed by FR167653. In addition FR167653 downregulated the expression of the adhesion molecules ICAM-1 and VCAM-1 (ELISA). FR167653 suppressed the development of a proinflamatory profile of HUVEC and human monocytes after stimulation with TNF-alpha or LPS, respectively. These results indicated anti-inflammatory properties of FR167653 on endothelial and inflammatory cells, which may be therapeutically useful to ameliorate vascular injury.

Apoptotic cell death during accelerated rejection in sensitized rat recipients of cardiac allografts.

Accelerated rejection due to host sensitization to major histocompatibility complex antigens is a critical problem in clinical organ transplantation in patients who have previously received an organ transplant, experienced acute rejection episodes, received blood transfusions, or been pregnant. The precise pathologic mechanisms underlying accelerated rejection have not been characterized. Herein, we describe apoptosis during T- and B-cell-driven accelerated rejection of cardiac allografts in presensitized recipients. In an established accelerated rejection model, Lewis rats were sensitized to skin grafts from Wistar-Furth rats; after 7 days, they received Wistar-Furth hearts. These grafts were rejected within 24 hours posttransplantation compared with 10 days in nonsensitized recipients (acute rejection, n = 5). Apoptosis was observed during accelerated rejection of cardiac allografts but not in naïve recipients of hearts, as demonstrated at DNA laddering and TUNEL (terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling) assay. Apoptosis was discovered as a thus far unknown effector mechanism in accelerated cardiac transplant rejection that accompanies combined cellular and humoral immune alloreactivity. Apoptotic cell death in accelerated rejection and the cascade of upstream and downstream events leading to or resulting from this process should be considered critical steps in the pathogenesis of accelerated rejection.

The influence of antigen-dependent and antigen-independent factors on the development of graft vasculopathy in a fully allogeneic cardiac allograft model in the rat.

Graft vasculopathy (GVP) is one of the major obstacles to long-term graft and patient survival after cardiac transplantation and a major reason for morbidity and mortality. Antigen-dependent and antigen-independent factors play causal roles in the development of GVP. The aim of this study was to evaluate antigen-dependent and -independent factors in the development of GVR in a clinically relevant fully allogeneic rat cardiac model under immunosuppression with cyclosporine (CyA). Lewis rats were challenged with Wistar-Furth cardiac allografts. Acute rejection occurred within 10 days after engraftment (n = 6). Daily SC administration of CyA (2.5 mg/kg body weight, n = 12) led to long-term graft survival (>100 days) but did not prevent GVP (Adams Score: 1.7 +/- 1.9, n = 4). Isografts did not develop GVP. In allografts, the dose modification of CyA to 5 mg or 1.25 mg/kg body weight as well as the prolongation of ischemia from 45 minutes to 4 hours did not increase the development of GVP. In isografts, the prolongation of ischemic time from 45 minutes to 4 hours significantly increased the development of GVP (Adams score, 0.3 +/- 0.8 [n = 7] vs 1.2 +/- 1.9 [n = 6]; P < .05). In this fully allogeneic cardiac allograft model with clinically relevant immunosuppressive therapy, GVP was induced independent of the applied CyA dose. In addition, the prolongation of ischemic time did not increase the development of GVP. Isografts only developed significant GVP with long ischemia times. Therefore, an initial injury, either prolonged ischemia time or an allogeneic immune response, predispressed to the development of GVP.

Severity of coronary artery disease but not degree of coronary stenosis is correlated to cerebrovascular reactivity.

BACKGROUND: A decade difference in peak incidences of coronary and cerebral ischemia assumes a protection of the brain vasculature. Therefore, we hypothesize that early indicators of cerebrovascular disease such as parameters of the neurovascular coupling show a higher correlation to coronary artery disease than morphologic parameters. METHODS: Stenotic degree (%) of coronary arteries (RCA, LCA, LAD, RCX) was determined together with the Gensini score by angiography in 96 patients (80 men; 62 +/- 10 years), which were grouped according to disease severity (sclerosis, 1-vessel disease (VD), 2-VD, 3-VD). Presence of internal carotid artery stenosis and left ventricular ejection fraction (LVEF) were established with duplex sonography. Resting and visually evoked hemodynamic responses were measured with transcranial Doppler ultrasound in both posterior cerebral arteries and expressed in terms of control system parameters. These were gain, natural frequency, attenuation, and rate time. Group differences and correlations between stenosis and parameters of vasoreactivity were tested. RESULTS: Groups differed in stenotic degree of coronary arteries, Gensini score, LVEF, carotid artery stenosis, resting flow velocity, and evoked responses (gain, p < 0.005; attenuation, p < 0.05). Stenosis of each coronary artery and LVEF were correlated to carotid artery stenosis but no association was found to cerebrovascular parameters. Only severity of coronary artery disease and the Gensini score were associated with disturbed cerebrovascular reactivity. Carotid artery stenosis was associated with decreased cerebrovascular parameters (attenuation, p < 0.05; rate time, p < 0.01). CONCLUSIONS: Although atherosclerosis is a systemic disease our data support concepts of a heterogeneous distribution of the disease indicating protection of brain vessels.

Beneficial effects of intravenously administered N-3 fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a prospective randomized study.

BACKGROUND: Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting operation (CABG). Experimental data have shown antiarrhythmic effects of n-3 polyunsaturated fatty acids (PUFA) on myocardial cells. Orally administered PUFA could significantly reduce the rate of postoperative AF. We assessed the efficacy of PUFA for the prevention of AF after CABG. PUFA were given intravenously to prevent variation in bioavailability. METHODS AND RESULTS: 52 patients were randomized to the interventional group, 50 served as controls. In the control group free fatty acids (100 mg soya oil/kg body weight/day) were infused via perfusion pump, starting on admission to hospital and ending at discharge from intensive care. In the interventional group PUFA were given at a dosage of 100 mg fish oil/kg body weight/day. Primary end point was the postoperative development of AF, documented by surface ECG. Secondary end point was the length of stay in the ICU. The demographic, clinical and surgical characteristics of the patients in the two groups were similar. Postoperative AF occurred in 15 patients (30.6 %) in the control and in 9 (17.3 %) in the PUFA group ( P < 0.05). After CABG, the PUFA patients had to be treated in the ICU for a shorter time than the control patients. No adverse effects were observed. CONCLUSIONS: Perioperative intravenous infusion of PUFA reduces the incidence of AF after CABG and leads to a shorter stay in the ICU and in hospital. Our data suggest that perioperative intravenous infusion of PUFA should be recommended for patients undergoing CABG.

New Findings in PiZZ alpha1-antitrypsin deficiency-related panniculitis. Demonstration of skin polymers and high dosing requirements of intravenous augmentation therapy.

Panniculitis is a recognized but unusual complication of a severe deficiency of alpha1-antitrypsin (AAT), with fewer than 100 cases described to date. Like the pathogenesis of emphysema in severe PiZZ deficiency of AAT, panniculitis has been hypothesized to be an inflammatory process, possibly related to Z AAT polymer formation and to an unopposed anti-inflammatory screen in the context of deficient serum levels of AAT. The current report presents a 31-year-old woman with PiZZ AAT deficiency-associated panniculitis. Our case extends current knowledge of AAT-associated panniculitis in 2 ways: (1) we demonstrate Z-type AAT polymers in the skin, which supports the inflammatory pathogenesis of panniculitis and the potential pro-inflammatory role of polymers; (2) we show that a high dose and long-term use of intravenous augmentation therapy (90 mg/kg body weight once weekly during 3 years) can ameliorate the frequency and severity of panniculitis associated with AAT deficiency.

[Vaginal prolapse and rectal obstruction. Treated with a vaginal vault mesh colpo suspension and laparoscopic resection rectopexy]. / Vaginalprolaps und Defäkationsobstruktion. Kombination einer Netzkolposuspension mit der laparoskopischen Resektionsrektopexie.

BACKGROUND: Stool outlet obstruction with incomplete or complete rectal prolapse combined with vaginal vault prolapse is a severe form of pelvic floor insufficiency. Combining laparoscopic resection rectopexy with a vaginal vault mesh colpo suspension is a possible way of correcting this defect. METHOD: The safety of the combination was evaluated in 18 patients. RESULTS: The procedure was performed successfully with no complications in 16 of the 18 patients. One patient suffered intraoperative rectal injury and therefore received no polypropylene mesh, and one showed intraoperative bleeding requiring transfusion. No secondary surgery was required. Hospital stay lasted an average of 11.4 days (range 8-20) and the urinary catheters could be removed after an average of 4.3 days (range 2-10). No urinary disturbances were noted at the time of hospital release. Short-term mild fever appeared in 28% of cases (5/18). There were two urinary tract infections. No disturbance in healing and no anastomotic insufficiency were observed. The duration of postoperative antibiotic therapy averaged 3 days (range 0-8). CONCLUSION: The combination of laparoscopic resection rectopexy with a vaginal vault mesh colpo suspension might be safe. The close contact between the mesh and anastomosis might induce no increase in insufficiency. Long-term outcome must still be evaluated.

Apigenin-induced nitric oxide production involves calcium-activated potassium channels and is responsible for antiangiogenic effects.

BACKGROUND: The dietary flavonoid apigenin (Api) has been demonstrated to exert multiple beneficial effects upon the vascular endothelium. The aim of this study was to examine whether Ca(2+)-activated K(+) channels (K(Ca)) are involved in endothelial nitric oxide (NO) production and antiangiogenic effects. METHODS: Endothelial NO generation was monitored using a cyclic guanosine monophosphate radioimmunoassay. K(Ca) activity and changes of the intracellular Ca(2+) concentration [Ca(2+)](i) were analyzed using the fluorescent dyes bis-barbituric acid oxonol, potassium-binding benzofuran isophthalate, and fluo-3. The endothelial angiogenic parameters measured were cell proliferation, [(3)H]-thymidine incorporation, and cell migration (scratch assay). Akt phosphorylation was examined using immunohistochemistry. RESULTS: Api caused a concentration-dependent increase in cyclic guanosine monophosphate levels, with a maximum effect at a concentration of 1 mum. Api-induced hyperpolarization was blocked by the small and large conductance K(Ca) inhibitors apamin and iberiotoxin, respectively. Furthermore, apamin and iberiotoxin blocked the late, long-lasting plateau phase of the Api-induced biphasic increase of [Ca(2+)](i). Inhibition of Ca(2+) signaling and the K(Ca) blockade both blocked NO production. Prevention of all three (NO, Ca(2+), and K(Ca) signaling) reversed the antiangiogenic effects of Api under both basal and basic fibroblast growth factor-induced culture conditions. Basic fibroblast growth factor-induced Akt phosphorylation was also reduced by Api. CONCLUSIONS: Based on our experimental results we propose the following signaling cascade for the effects of Api on endothelial cell signaling. Api activates small and large conductance K(Ca), leading to a hyperpolarization that is followed by a Ca(2+) influx. The increase of [Ca(2+)](i) is responsible for an increased NO production that mediates the antiangiogenic effects of Api via Akt dephosphorylation.

Planar polarity of root hair positioning in Arabidopsis.

The co-ordinated polarity of cells within the plane of a single tissue layer (planar polarity) is intensively studied in animal epithelia but has only recently been systematically analysed in plants. The polar positioning of hairs in the root epidermis of Arabidopsis thaliana provides an easily accessible system for the functional dissection of a plant-specific planar polarity. Recently, mutants originally isolated in genetic screens for defects in root hair morphogenesis and changes in the sensitivity to or the production of the plant hormones auxin and ethylene have identified players that contribute to polar root hair placement. Here, we summarize and discuss recent progress in research on polar root hair positioning from studies in Arabidopsis.

Elevated Lipoprotein(a) does not promote early atherosclerotic changes of the carotid arteries in young, healthy adults.

BACKGROUND: Elevated levels of Lipoprotein(a) [Lp(a)] have been linked to an increased risk of ischemic cardiovascular events. Yet the mechanism by which Lp(a) might contribute to this increased risk is not clear. METHODS: To elucidate whether high plasma levels of Lp(a) contribute to the development of early atherosclerotic vessel wall changes, the intima-media thickness of the common carotid arteries [CCA-IMT] of 151 healthy young volunteers without additional relevant cardiovascular risk factors was measured by high-resolution ultrasound. Plasma concentrations of Lp(a) were quantified and other established risk factors, such as body mass index [BMI], plasma levels of cholesterol, triglycerides and homocysteine, were determined. Furthermore, the carotid arteries were examined for the presence of plaques and stenoses. RESULTS: Univariate analysis showed a significantly negative correlation of CCA-IMT with HDL cholesterol and positive correlations with age, BMI, total and LDL cholesterol, triglycerides and even with homocysteine, but not with Lp(a). When the study population was dichotomized according to Lp(a) levels, no statistically significant differences in CCA-IMT could be detected between persons with plasma Lp(a)<300mg/l or >or=300mg/l, respectively. CONCLUSION: Our data suggest that elevated Lp(a) levels alone do not contribute to increased cardiovascular risk by promoting early atherogenesis in vivo.

Changes in extracranial arteries in obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is linked with increased cardiovascular morbidity and mortality, possibly through an enhancement of atherosclerotic vascular changes. Up to now, however, only a few studies have tried to evaluate the occurrence of atherosclerosis in patients with OSA. In the present study, ultrasonography of the large extracranial vessels was performed in a group of consecutively admitted OSA patients (n = 35) and a control group of non-OSA patients (n = 35). Common carotid artery-intima media thickness (CCA-IMT) was measured at the far wall of both proximal carotid arteries. Furthermore, the presence of plaques and stenoses of the extracranial vessels was determined. All measurements were carried out blinded to the status of the patients. In the OSA group, CCA-IMT was significantly increased when compared with the non-OSA patients and was related to the degree of nocturnal hypoxia. Additionally, the formation of plaques was more pronounced and extracranial vessel stenosis was more common in the OSA patients. In conclusion, these findings are in favour of an independent influence of obstructive sleep apnoea on atherosclerotic changes of the arterial wall, and represent further strong arguments for obstructive sleep apnoea being a risk factor on its own for the emergence of cardiovascular disease.

[Persistent angina pectoris in spite of successful myocardial revascularisation]. / Fortbestehende Angina pectoris trotz erfolgreicher Myokardrevaskularisation.

A 73-year-old obese woman underwent coronary artery-bypass operation in 11/1995 because of a coronary two vessel disease. The left coronary artery was bypassed by the left mammarial internal artery. In 2 and 3/2002, balloon-dilatation of stenoses of the right coronary artery and the circumflex was performed. Angina pectoris relapsed and in 9/2002 the patient was admitted to our hospital with tentative diagnosis of restenosis. Physical investigation showed a blood pressure of the right arm of 160/80 and of the left arm of 120/ 80 mmHg. Coronarography showed the three vessel disease known since 2/2002 with a restenosis of the right coronary artery which was immediately treated by balloon-dilatation and stent-implantation. Colour duplex-sonography of the carotid and subclavian arteries revealed extraordinary plaques and a reduced flow of the left vertebral artery. The left subclavian artery could only be seen distal to the discharge of the vertebral artery and showed a poststenotic flow. The patient had angina pectoris when carrying out personal hygiene already 2 days after balloon-dilatation and stent-implantation. ECG showed new aspects. Coronarography showed no relapse of stenosis, but 70% stenosis of the left subclavian artery with a marked coronary-steal-syndrome. In 10/ 2002, the patient underwent balloon-dilatation and stent-implantation of the subclavian stenosis and became free of complaints. Coronary-steal-syndrome can be the reason for persistent angina pectoris in spite of successful coronary artery-bypass operation with a mammarial internal bypass. It is absolutely necessary to take blood pressure from both arms to recognise a possible stenosis of the subclavian artery which can be the key to all.

Functional characterization of the KNOLLE-interacting t-SNARE AtSNAP33 and its role in plant cytokinesis.

Cytokinesis requires membrane fusion during cleavage-furrow ingression in animals and cell plate formation in plants. In Arabidopsis, the Sec1 homologue KEULE (KEU) and the cytokinesis-specific syntaxin KNOLLE (KN) cooperate to promote vesicle fusion in the cell division plane. Here, we characterize AtSNAP33, an Arabidopsis homologue of the t-SNARE SNAP25, that was identified as a KN interactor in a yeast two-hybrid screen. AtSNAP33 is a ubiquitously expressed membrane-associated protein that accumulated at the plasma membrane and during cell division colocalized with KN at the forming cell plate. A T-DNA insertion in the AtSNAP33 gene caused loss of AtSNAP33 function, resulting in a lethal dwarf phenotype. atsnap33 plantlets gradually developed large necrotic lesions on cotyledons and rosette leaves, resembling pathogen-induced cellular responses, and eventually died before flowering. In addition, mutant seedlings displayed cytokinetic defects, and atsnap33 in combination with the cytokinesis mutant keu was embryo lethal. Analysis of the Arabidopsis genome revealed two further SNAP25-like proteins that also interacted with KN in the yeast two-hybrid assay. Our results suggest that AtSNAP33, the first SNAP25 homologue characterized in plants, is involved in diverse membrane fusion processes, including cell plate formation, and that AtSNAP33 function in cytokinesis may be replaced partially by other SNAP25 homologues.

Cell axiality and polarity in plants--adding pieces to the puzzle.

Plant cell polarity is important for cellular function and multicellular development. Classical physiological and cell biological analyses identified cues that orient cell polarity and suggested molecules that translate a cue into intracellular asymmetry. A range of proteins that either mark or are involved in the establishment of a (polar) axis are now available, as are many relevant mutants. These tools are likely to facilitate a dissection of the molecular mechanisms behind cell and organ polarity in the near future.

Tamoxifen sensitivity-testing of glioblastomas: comparison of in vitro and in vivo results.

BACKGROUND: Only less than half of the patients with malignant gliomas respond to a continuous high dose Tamoxifen (TAM) and/or Carboplatin (CP)-treatment. Therefore, a method for predicting the efficacy of TAM-treatment would be desirable. METHODS: Paralleling a clinical study, the predictive value of in vitro-sensitivity testing of TAM and TAM's metabolite 4-OH-TAM in primary cultures of tumour explants from 15 of a total of 50 patients was examined. Additionally, the influence of TAM, 4-OH-TAM, and CP on the proliferation of established glioblastoma cell lines and of those explanted from athymic nude mice and re-established in cell culture was investigated. Human glioblastomas xenotransplanted subcutaneously into athymic nude mice and subsequently treated with TAM and/or CP were examined in a parallel in vivo-study. FINDINGS: TAM-chemosensitivity-testing of glioblastomas failed to predict the clinical response to TAM-treatment in our patients and did not correlate with the in vivo-TAM-response of tumours xenotransplanted into nude mice. TAM's and 4-OH-TAM's ability to inhibit growth of various glioblastoma cell lines in vitro in very similar concentrations was shown to be a consistent phenomenon which seems to be independent of the in vivo response in either patients or mice as previous hosts. However, CP's antiproliferative effect on glioblastomas in vivo was paralleled by respective in vitro results. Whereas TAM showed to mediate its in vitro antiproliferative effect by inducing apoptosis in most cell lines examined, CP-treatment lead to necrosis of cells. INTERPRETATION: Combining the results obtained from our human and mouse studies, it has to be postulated that host factors other than the sensitivity to TAM of the individual cell, determine the efficacy of TAM-treatment in vivo.