Association between the blood pressure response to a change in posture and the 6-year incidence of hypertension: prospective findings from the ARIC study

The association between the blood pressure response to a change from the supine to the standing position and the 6-year incidence of hypertension was studied in a bi-ethnic, middle-aged cohort of 6951 normotensive men and women free of coronary heart disease at baseline. Postural change in systolic blood pressure (SBP) was categorized into deciles, and the middle four deciles served as the referent (no change) group. In unadjusted analyses, the incidence of hypertension was higher among both those with SBP increases and decreases relative to those in the referent group. Associations were modestly attenuated after controlling for age, ethnicity, and gender and cardiovascular disease risk factors. However, after adjustment for baseline, seated SBP, a modest association with incident hypertension persisted only for SBP decreases. Orthostatic hypotension (upon standing) was associated with incident hypertension and isolated systolic hypertension and, unexpectedly, this increased risk was highest among those with the lowest levels of baseline, resting SBP.     

Deep brain stimulation of the subthalamic nucleus versus levodopa challenge in Parkinson's disease: measuring the on- and off-conditions with FDG-PET

Summary. In order to compare the effects of high-frequency stimulation of the subthalamic nucleus (STN-DBS) and a levodopa-challenge on cerebral metabolic activity, we conducted PET scans with [¹⁸F]2-fluoro-2-deoxyglucose (FDG) in the drug- and stimulation- on- and off-condition in a single patient suffering from advanced PD. Our data revealed evidence for improved thalamocortical processing released from inhibition by overactive basal ganglia output nuclei in both on-conditions. While levodopa also led to a reduction of lentiform hyperactivity, effective STN stimulation seemed to interfere with distinct cerebellar and limbic circuits. Received November 2, 2001; accepted January 15, 2002 Published online June 28, 2002     

Stenosen und Verschlüsse der supraaortalen Gefäße – interdisziplinäre interventionelle Behandlung von Patienten mit erhöhtem Operationsrisiko

PURPOSE: The value of elective PTA in stenoses of the supraaortic vessels and especially of the carotid artery is still under discussion. Stenoses after surgical and/or radiation therapy and a high cardio-vascular risk for a surgical procedure, however, justify minimal-invasive techniques. MATERIAL AND METHODS: In 31 patients with 24 symptomatic and 7 asymptomatic stenoses of the supraaortic arteries (3 Acc, 19 Aci, 5 Ascl, 4 Tr.brc, 2 Aax) minimal-invasive angioplasty and stent-placement was performed. The rationale for the interventional procedure was an elevated medical or technical risk of the respective surgical procedure. All procedures were performed using a coaxial technique with a guiding catheter. An open vascular access was necessary in 7 cases due to an unfavorable anatomical situation. RESULTS: The technical success rate was 100%. Peri-interventionally, a TIA occurred in 2 patients (1 spontaneous relieve, 1 complete remission after rt-PA lysis therapy). During the mean follow-up period of 13 months 3 patients died due to non-cerebrovascular reasons. In 2 patients a moderate restenosis, in 1 a high-grade stenosis, and in 1 and complete occlusion occurred without symptoms. After one year of follow-up, all treated stenoses were patent with a restenosis rate of 10.7% without further neurological symptoms. CONCLUSION: Interventional angioplasty with stent-placement of the supraaortic arteries is a safe and effective alternative in patients are at high risk for classical surgical procedures.     

Symptomatic vertebral hemangiomas: treatment by means of direct intralesional injection of ethanol

PURPOSE: To describe the technique and results of injecting ethanol directly into symptomatic vertebral hemangiomas. MATERIALS AND METHODS: Eleven patients with paraplegia (n = 6) or radiculopathy (n = 5) due to vertebral hemangioma were treated by means of injecting ethanol (5-50 mL) directly into the lesion with computed tomographic (CT) guidance. CT angiograms were essential prior to treatment to identify functional vascular spaces of the hemangioma and direct needle placement. RESULTS: All hemangiomas were obliterated completely at follow-up angiography and gadolinium-enhanced magnetic resonance imaging. Five of six patients with paraplegia recovered completely: One who was treated recently was walking with assistance. Four of five patients with radiculopathy improved. No immediate complications were associated with ethanol injection. The two patients who received the largest volumes of ethanol, 42 and 50 mL, developed pathologic fractures of the involved vertebrae 4 and 16 weeks after treatment. CONCLUSION: Direct injection of ethanol into symptomatic vertebral hemangioma is an effective and safe treatment, provided the dose is less than 15 mL.     

Expression of late cell cycle genes and an increased proliferative capacity characterize very early relapse of childhood acute lymphoblastic leukemia.

PURPOSE: In childhood acute lymphoblastic leukemia (ALL), approximately 25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors (i.e., time and site of relapse, immunophenotype, and minimal residual disease). However, the underlying biological determinants of these prognostic factors remain poorly understood. EXPERIMENTAL DESIGN: Aiming at identifying molecular pathways associated with these clinically well-defined prognostic factors, we did gene expression profiling on 60 prospectively collected samples of first relapse patients enrolled on the relapse trial ALL-REZ BFM 2002 of the Berlin-Frankfurt-Münster study group. RESULTS: We show here that patients with very early relapse of ALL are characterized by a distinctive gene expression pattern. We identified a set of 83 genes differentially expressed in very early relapsed ALL compared with late relapsed disease. The vast majority of genes were up-regulated and many were late cell cycle genes with a function in mitosis. In addition, samples from patients with very early relapse showed a significant increase in the percentage of S and G(2)-M phase cells and this correlated well with the expression level of cell cycle genes. CONCLUSIONS: Very early relapse of ALL is characterized by an increased proliferative capacity of leukemic blasts and up-regulated mitotic genes. The latter suggests that novel drugs, targeting late cell cycle proteins, might be beneficial for these patients that typically face a dismal prognosis.     

Minimal residual disease in gastric cancer: evidence of an independent prognostic relevance of urokinase receptor expression by disseminated tumor cells in the bone marrow.

PURPOSE: To study the invasion-related molecule urokinase-type plasminogen activator receptor (u-PAR) expressed by disseminated tumor cells as a biologic predictor of poor survival in a large prospective series of patients with gastric cancer. PATIENTS AND METHODS: In 156 gastric cancer patients (prospective series), disseminated tumor cells in the bone marrow and the u-PAR expressed by these tumor cells were determined by cytokeratin (CK) 18 immunocytochemistry and u-PAR/CK18 double immunocytochemistry. RESULTS: In contrast to the mere detection of disseminated tumor cells at primary surgery, the additional evidence of u-PAR on these cells correlated significantly with pathologic T stage (P =.0474) and the expression of u-PAR (P =.0093) and plasminogen-activator inhibitor 1 (P =.0145) in the primary tumor (immunohistochemistry, chi(2)). Kaplan-Meier analysis revealed no association with prognosis for the mere detection of disseminated tumor cells. In contrast, a significant association was seen between detection of u-PAR on these cells and shorter disease-free (P <.0001) and overall survival (P <.0001). Multivariate analysis revealed that u-PAR on disseminated tumor cells at the time of primary surgery is an independent prognostic factor for disease-free (95% confidence interval [CI], 1.72 to 3.21; P =.024) and overall survival (P =.0049; relative risk, 2.89; 95% CI, 1.92 to 4.30). CONCLUSION: This is the first large study to show that u-PAR, detected on disseminated tumor cells in the bone marrow, is an independent prognostic parameter in gastric cancer, in contrast to the mere detection of minimal residual disease (MRD). u-PAR may be a promising marker to define a critical subpopulation of disseminated tumor cells and a target to eliminate MRD. Molecular phenotyping of MRD is critical for defining its individual clinical relevance.     

Angiogenesis and Brain Oedema in Intracranial Meningiomas: Influence of Vascular Endothelial Growth Factor

Summary The correlation between angiographic neovascularization, peritumoural brain oedema (PTBOe) and the expression of vascular endothelial growth factor (VEGF) , was analysed in 30 patients with intracranial meningiomas. Pre-operative angiograms were examined for the existence of either an exclusively dural tumour blush or an additionally pial tumour supply from cerebral arteries. Furthermore the presence of macroscopic tumour-neovascularization and dysplastic changes of tumour-draining cerebral veins was evaluated. VEGF expression was investigated on histological tissue samples, using immunohistochemical techniques. VEGF immunohistochemistry and neuroradiological evaluations were performed in double blind fashion. Tumour volume and the amount of oedema were calculated by computerized tomography (CT) or magnetic resonance imaging (MRI). The oedema-tumour volume ratio was defined as oedema index (OeI). Compared to VEGF-negative meningiomas, tumours with striking VEGF staining revealed a significant higher mean oedema index (OeI=4,2 vs. OeI=1,5; p<0.018), and a higher oedema incidence (91,7% vs. 44,4%; p<0.046). Equally, meningiomas with additionally tumour supply from cerebral arteries were associated with a significant higher mean OeI (OeI=4.1 vs. OeI=1.2; p<0.01) and oedema incidence (94,7% vs. 20,0%; p<0,0023) than meningiomas with exclusively tumour supply from dural arteries. All meningiomas with striking VEGF-expression were associated with vascular tumour supply from cerebral arteries, but VEGF-negative tumours only in 50% (p<0.029). These data suggest a link between VEGF-expression, arterial tumour supply and peritumoural brain oedema. The development of tumour supply from cerebral arteries may be important for formation of meningioma-related oedema. Therefore, VEGF may represent a potent mediator in the evolution of this type of vascularization in meningiomas.     

EEG frequency analysis in the course of acute ischemic stroke

Summary In 18 patients with acute cerebrovascular disease (17 ischemic, 1 hemorrhagic stroke) neurological symptoms were scored repeatedly using a rating scale for disturbance of consciousness, motor dysfunctions, disturbance of higher cortical functions, abnormalities of cranial nerves, and impairment of sensations, and related to EEG-abnormalities quantified by frequency analysis. A correspondence between location of neurologic lesion and EEG focus was found in 87%, but correlation between neurologic score and the degree of EEG-abnormality was low. Changes of clinical defects were not significantly related to various quantified EEG parameters. These results suggest that computerized EEG analysis has to be used with caution for quantifying the clinical course of stroke patients.Dedicated to Professor K. J. Zülch on the occasion of his 70th birthday.