Medical graphics to improve patient understanding and anxiety in elderly and cognitively impaired patients scheduled for transcatheter aortic valve implantation (TAVI).

BACKGROUND: Anxiety and limited patient comprehension may pose significant barriers when informing elderly patients about complex procedures such as transcatheter aortic valve implantation (TAVI). OBJECTIVES: We aimed to evaluate the utility of medical graphics to improve the patient informed consent (IC) before TAVI. METHODS: In this prospective, randomized dual center study, 301 patients were assigned to a patient brochure containing medical graphics (Comic group, n = 153) or sham information (Control group, n = 148) on top of usual IC. Primary outcomes were patient understanding of central IC-related aspects and periprocedural anxiety assessed by the validated Spielberger State Trait Anxiety Inventory (STAI), both analyzed by cognitive status according to the Montreal Cognitive Assessment (MoCA). RESULTS: Patient understanding was significantly higher in the Comic group [mean number of correct answers 12.8 (SD 1.2) vs. 11.3 (1.8); mean difference 1.5 (95% CI 1.2-1.8); p < 0.001]. This effect was more pronounced in the presence of cognitive dysfunction (MoCA < 26) [12.6 (1.2) in the Comic vs. 10.9 (1.6) in the Control group; mean difference 1.8 (1.4-2.2), p < 0.001]. Mean STAI score declined by 5.7 (95% CI 5.1-6.3; p < 0.001) in the Comic and 0.8 points (0.2-1.4; p = 0.015) in the Control group. Finally, mean STAI score decreased in the Comic group by 4.7 (3.8-5.6) in cognitively impaired patients and by 6.6 (95% CI 5.8 to 7.5) in patients with normal cognitive function (p < 0.001 each). CONCLUSIONS: Our results prove beneficial effects for using medical graphics to inform elderly patients about TAVI by improving patient understanding and reducing periprocedural anxiety (DRKS00021661; 23/Oct/2020). Medical graphics entailed significant beneficial effects on the primary endpoints, patient understanding and periprocedural anxiety, compared to the usual patient informed consent (IC) procedure. Patient understanding of IC-related aspects was significantly higher in the Comic group, with a more pronounced benefit in patients with cognitive impairment (p for IC method and cognitive status < 0.001, respectively; p for IC method x MoCA category interaction = 0.017). There further was a significant decline of periprocedural anxiety in patients with and without cognitive impairment (p for IC method x measuring time point < 0.001; p for IC method x MoCA category x measuring time point interaction = 0.018).

2-(4-(Biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52)--a novel type of 5-lipoxygenase inhibitor with favourable molecular pharmacology and efficacy in vivo.

BACKGROUND AND PURPOSE: 5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes (LTs) representing a potential target for pharmacological intervention with inflammation and allergic disorders. Although many LT synthesis inhibitors are effective in simple in vitro test systems, they frequently fail in vivo due to lack of efficacy. Here, we attempted to assess the pharmacological potential of the previously identified 5-LO inhibitor 2-(4-(biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52). EXPERIMENTAL APPROACH: We evaluated the efficacy of HZ52 in vivo using carrageenan-induced pleurisy in rats and platelet-activating factor (PAF)-induced lethal shock in mice. We also characterized 5-LO inhibition by HZ52 at the cellular and molecular level in comparison with other types of 5-LO inhibitor, that is, BWA4C, ZM230487 and hyperforin. KEY RESULTS: HZ52, 1.5 mg·kg⁻¹ i.p., prevented carrageenan-induced pleurisy accompanied by reduced LTB(4) levels and protected mice (10 mg·kg⁻¹, i.p.) against PAF-induced shock. Detailed analysis in cell-based and cell-free assays revealed that inhibition of 5-LO by HZ52 (i) does not depend on radical scavenging properties and is reversible; (ii) is not impaired by an increased peroxide tone or by elevated substrate concentrations; and (iii) is little affected by the cell stimulus or by phospholipids, glycerides, membranes or Ca²âº. CONCLUSIONS AND IMPLICATIONS: HZ52 is a promising new type of 5-LO inhibitor with efficacy in vivo and with a favourable pharmacological profile. It possesses a unique 5-LO inhibitory mechanism different from classical 5-LO inhibitors and seemingly lacks the typical disadvantages of former classes of LT synthesis blockers.

Sources and Delivery of Nutrients to the Northwestern Gulf of Mexico from Streams in the South-Central United States.

SPAtially Referenced Regressions On Watershed attributes (SPARROW) models were developed to estimate nutrient inputs [total nitrogen (TN) and total phosphorus (TP)] to the northwestern part of the Gulf of Mexico from streams in the South-Central United States (U.S.). This area included drainages of the Lower Mississippi, Arkansas-White-Red, and Texas-Gulf hydrologic regions. The models were standardized to reflect nutrient sources and stream conditions during 2002. Model predictions of nutrient loads (mass per time) and yields (mass per area per time) generally were greatest in streams in the eastern part of the region and along reaches near the Texas and Louisiana shoreline. The Mississippi River and Atchafalaya River watersheds, which drain nearly two-thirds of the conterminous U.S., delivered the largest nutrient loads to the Gulf of Mexico, as expected. However, the three largest delivered TN yields were from the Trinity River/Galveston Bay, Calcasieu River, and Aransas River watersheds, while the three largest delivered TP yields were from the Calcasieu River, Mermentau River, and Trinity River/Galveston Bay watersheds. Model output indicated that the three largest sources of nitrogen from the region were atmospheric deposition (42%), commercial fertilizer (20%), and livestock manure (unconfined, 17%). The three largest sources of phosphorus were commercial fertilizer (28%), urban runoff (23%), and livestock manure (confined and unconfined, 23%).

Stereotactic aspiration and fibrinolysis of spontaneous supratentorial intracerebral hematomas versus conservative treatment: a matched-pair study.

OBJECTIVES: Since introduction of stereotactic aspiration and fibrinolysis into the treatment of deep-seated intracerebral hematomas by Hondo and Matsumoto 1984 this method has become widely used, and satisfactory morphological results are achieved. Nevertheless, whether the outcome is improved has not yet been investigated. MATERIAL AND METHOD: 17 patients with spontaneous intracerebral hematomas have been treated surgically; after angiographic exclusion of a vascular malformation stereotactic aspiration and fibrinolysis with 3 mg rTPA was performed. Between 1992 and 1995 104 patients were treated conservatively according to best medical treatment. From this group "matched pairs" with the surgical patients were set up concurring in primary (consciousness, size and location of the hematoma) and secondary parameters (age, sex, ventricular hemorrhage). Endpoint of the study was the Glasgow outcome score (GOS) six months after treatment. Data were analyzed statistically and p < 0.05 was considered significant. RESULTS: In respect of primary parameters complete concurrence and regarding secondary parameters far-reaching concurrence was achieved. In no parameter the surgical and conservative group were significantly different from each other. Six months after the ictus no significant difference between surgical and conservative treatment concerning GOS could be established. CONCLUSION: These results indicate that patients do not benefit from stereotactic aspiration and fibrinolysis of putamenal hematomas. For a final treatment recommendation a prospective randomised trial is required.

The voice of emotional memory: content-filtered speech in panic disorder, social phobia, and major depressive disorder.

We asked patients with either panic disorder, social phobia, or major depressive disorder and healthy control participants to describe their most frightening experience and to describe an emotionally neutral experience. Both fear and neutral autobiographical memories were audiotaped and processed through a low-pass filter that eliminated frequencies above 400 Hz, thereby abolishing semantic content but leaving paralinguistic aspects like rate, pitch, and loudness intact, and these convey emotional cues. Raters blind to content and diagnosis rated the content-filtered speech clips on emotional dimensions. The results revealed that content-filtered fear memories received significantly higher ratings on anxious, aroused, and dominant (but not sad or negative) scales than did content-filtered neutral memories, irrespective of the diagnostic status of the speaker. Content-filtered speech appears promising as an on-line probe of emotional processing during accessing of autobiographical memories.

[A patient with Gulf war syndrome. On discussion of an uncertain disease picture]. / Ein Patient mit Golfkriegssyndrom? Zur Diskussion eines unklaren Krankheitsbildes.

The Gulf War syndrome represents neurological and neuropsychological disorders in veterans of the Persian Gulf war. Until today, the various symptoms observed could not be attributed to any defined disease. As a possible cause, exposure to neurotoxic agents such as the organophosphates used during the war has been suggested by many authors. We report on a 29-year-old man who suffered from dysmnesia, disturbance of orientation, cognitive impairment, and double vision. His history revealed several front-line operations in 1990 and 1991 during the Gulf War. Physical examinations showed a complex eye-movement disturbance and a horizontal nystagmus, which was neuro-ophthalmologically confirmed. The early auditory potentials referred to a brainstem dysfunction and the cognitive disturbances correlated to changes in the late-appearing component of event-related potentials (P 300). Brain imaging with CCT, MRI, SPECT, PET, and EEG and CSF showed no pathologies. Neuropsychological tests disclosed severe cognitive impairment especially concerning memory. Three-month follow-up studies in a department of psychosomatic medicine excluded a dissociative disorder as a feature of a post-traumatic stress or a conversion disorder. This is the first case of Gulf War syndrome in Germany. We focus on an unfamiliar complication after the war. The recent literature is reviewed.

Poor responder-high responder: the importance of soluble vascular endothelial growth factor receptor 1 in ovarian stimulation protocols.

This study was designed to detect vascular endothelial growth factor (VEGF) and its soluble receptor (sVEGFR-1) in follicular fluid specimens and to evaluate the importance of sVEGFR-1 with respect to ovarian response to gonadotrophin stimulation. A total of 69 patients was treated for IVF with recombinant human follicle stimulating hormone (FSH). Concentrations of VEGF and sVEGFR-1 were quantified in follicular fluids from oocyte retrievals. Patients were designated to three groups with respect to the number of harvested oocytes: group A, 1-5 oocytes; group B, 6-10 oocytes; group C, >10 oocytes. In group A, 1133 +/- 870 pg VEGF/ml follicular fluid per oocyte were quantified, in group B 426 +/- 262 pg VEGF/ml per oocyte, and in group C 274 +/- 179 pg VEGF/ml per oocyte. Soluble VEGFR-1 concentrations resulted in 1200 +/- 523 pg/ml follicular fluid per oocyte in group A, 255 +/- 193 pg/ml per oocyte in group B, and 79 +/- 69 pg/ml per oocyte in group C. No free sVEGFR-1 could be detected in any follicular fluid. An index to estimate the biological activity of VEGF by dividing VEGF/sVEGFR-1 revealed an increasing availability of VEGF with higher ovarian response to gonadotrophin therapy. In group A this index was 1.03, in group B 1.71, and in group C 3.21. A delicate balance between VEGF and sVEGFR-1 is necessary to allow an adequate ovarian reaction to gonadotrophin therapy. Excess of bio-active VEGF increases the risk for ovarian hyperstimulation syndrome. Excess of sVEGFR-1 results in poor response and goes in parallel with reduced chances for conception.

Expression of vascular endothelial growth factor receptors 1, 2 and 3 in placentas from normal and complicated pregnancies.

Extensive angiogenesis and invasion of the maternal decidua by trophoblasts are essential for the development and function of the placenta. Vascular endothelial growth factors (VEGF), placenta growth factor (PlGF) and their receptors VEGFR-1/Flt-1, VEGFR-2/KDR and VEGFR-3/Flt4 have important roles in vasculogenesis and angiogenesis. We have studied the localization of these proteins by immunohistochemistry and Western blotting in the placenta and of PlGF in maternal serum, and their association with diabetes, pre-eclampsia, fetal growth restriction (FGR) and fetal alcohol syndrome (FAS). VEGFR-1 and VEGFR-3 were detected mainly in the syncytiotrophoblastic layer whereas VEGFR-2 was detected in the vascular endothelial cells of the placenta. VEGFR-1, but not the other receptors, showed increased expression in placental syncytiotrophoblasts from 50% of patients with severe pre-eclampsia and FGR when compared with normal placentas. PlGF was undetectable in 38 of 44 samples of amniotic fluid of mothers with normal and complicated pregnancies. However, maternal serum PlGF concentrations were significantly lower in pre-eclamptic patients and in those with FGR when compared to diabetic women or healthy controls. These results suggest that low maternal serum PlGF and increased placental expression of its receptor VEGFR-1 are associated with pre-eclampsia and FGR.

Involvement of VEGFR-2 (kdr/flk-1) but not VEGFR-1 (flt-1) in VEGF-A and VEGF-C-induced tube formation by human microvascular endothelial cells in fibrin matrices in vitro.

Different forms of vascular endothelial growth factor (VEGF) and their cellular receptors (VEGFR) are associated with angiogenesis, as demonstrated by the lethality of VEGF-A, VEGFR-1 or VEGFR-2 knockout mice. Here we have used an in vitro angiogenesis model, consisting of human microvascular endothelial cells (hMVEC) cultured on three-dimensional (3D) fibrin matrices to investigate the roles of VEGFR-1 and VEGFR-2 in the process of VEGF-A and VEGF-C-induced tube formation. Soluble VEGFR-1 completely inhibited the tube formation induced by the combination of VEGF-A and TNF alpha (VEGF-A/TNF alpha). This inhibition was not observed when tube formation was induced by VEGF-C/TNF alpha or bFGF/TNF alpha. Blocking monoclonal antibodies specific for VEGFR-2, but not antibodies specifically blocking VEGFR-1, were able to inhibit the VEGF-A/TNF alpha-induced as well as the VEGF-C/TNF alpha-induced tube formation in vitro. P1GF-2, which interacts only with VEGFR-1, neither induced tube formation in combination with TNF alpha, nor inhibited or stimulated by itself the VEGF-A/TNF alpha-induced tube formation in vitro. These data indicate that VEGF-A or VEGF-C activation of the VEGFR-2, and not of VEGFR-1, is involved in the formation of capillary-like tubular structures of hMVEC in 3D fibrin matrices used as a model of repair-associated or pathological angiogenesis in vitro.

Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids.

One of the key molecules promoting angiogenesis is the endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF or VEGF-A), which acts through two high-affinity receptor tyrosine kinases (VEGFR), VEGFR-1 (or Flt-1) and VEGFR-2 (or KDR/Flk-1). It was shown before that a soluble variant of VEGFR-1 (sVEGFR-1) can be generated by differential splicing of the flt-1 mRNA. This soluble receptor is an antagonist to VEGF action, reducing the level of free, active VEGF-A, and therefore, plays a pivotal role in the generation of vascular diseases like pre-eclampsia or intra-uterine growth retardation. Here we show that sVEGFR-1 is produced by cultured human microvascular and macrovascular endothelial cells and a human melanoma cell line. The soluble receptor is mainly complexed with ligands; only 5-10% remains detectable as free, uncomplexed receptor protein. Furthermore, we show the time course of total and free sVEGFR-1 release together with its putative ligands, VEGF-A and placenta growth factor (PIGF), from macrovascular endothelial cells. The release of sVEGFR-1 was quantitatively measured in two different ELISA types. The release of sVEGFR-1 was strongly enhanced by phorbol-ester (PMA); the cells produced up to 22 ng/ml of sVEGFR-1 after 48 hours. The expression of VEGF-A and PIGF was moderately influenced by PMA. We also show a hypoxia-induced increase of sVEGFR-1 expression in cells cultured from placenta, a tissue that has a high flt-1 gene expression. Moreover, we demonstrate that sVEGFR-1 in amniotic fluids acts as a sink for exogenous VEGF165 and PIGF-2. Here, for the first time, to what extent recombinant ligands have to be added to compensate for the sink function of amniotic fluids was analyzed. In conclusion, human endothelial cells produce high levels of sVEGFR-1, which influences the availability of VEGF-A or related ligands. Therefore, sVEGFR-1 may reduce the ligand binding to transmembrane receptors and interfere with their signal transduction.

Amniotic fluid--soluble vascular endothelial growth factor receptor-1 in preeclampsia.

OBJECTIVE: To measure the levels of the soluble receptor for the potent angiogenic agent vascular endothelial growth factor (VEGF) in amniotic fluid (AF) in healthy and complicated pregnancies, and compare them with levels of erythropoietin, another factor upregulated by hypoxia. METHODS: We assessed amniotic fluid from the second (n = 35, gestational weeks 14-19) and third (n = 29) trimesters of healthy women, and from the third trimesters of preeclamptic (n = 22) and diabetic women with (n = 11) or without preeclampsia (n = 34) and from women with fetal growth restriction (FGR) (n = 14) for soluble VEGF receptor-1 (VEGFR-1) by enzyme-linked immunosorbent assay. RESULTS: In early normal pregnancy, AF-soluble VEGFR-1 levels were higher (median 22 ng/mL, range 2.3-29.5 ng/mL) than in the third trimester (median 13 ng/mL, range 0.5-32 ng/mL; P < .05). In preeclamptic women during the third trimester, levels were higher (median 20 ng/mL, range 10.5-37 ng/mL; P < .05) than healthy controls. The lowest third-trimester levels were in diabetic women (median 11 ng/mL, range 0.5-27 ng/mL). In women with preeclampsia and diabetes, AF-soluble VEGFR-1 levels remained lower (median 13, range 6-32 ng/mL; P < .05) than in women with preeclampsia alone. Amniotic fluid levels of soluble VEGFR-1 in women with FGR (median 19.5 ng/mL, range 5-40 ng/mL) did not statistically differ from those of controls. The AF levels of soluble VEGFR-1 did not correlate with those of erythropoietin. Soluble VEGFR-1 was clearly detectable (median 14 ng/mL, range 9-22 ng/mL) in culture media from placental biopsies (n = 20). CONCLUSION: Preeclampsia is associated with increased levels of soluble VEGFR-1, which are independent of erythropoietin, another hypoxia-inducible factor.

Is panic disorder linked to cognitive avoidance of threatening information?

We used a directed-forgetting paradigm to investigate whether panic disorder patients cognitively avoid threatening information. To determine if hemispheric laterality predicts processing biases in this paradigm, we used dichotic listening methods to ascertain participants' auditory perceptual asymmetry (PA). Panic disorder patients and healthy control participants viewed a series of intermixed threat, positive, and neutral words, each followed by an instruction to either remember the word or forget it. They then performed free recall and recognition tests for all words, irrespective of initial instructions. Directed-forgetting effects occurred equally for all word types: both groups recalled remember-words better than forget-words. Because this task is strongly affected by encoding style, panic patients as a group do not seem to avoid encoding threat cues. However, PA analyses revealed that cognitive avoidance of threat forget-words was significantly associated with greater left hemisphere bias in the control group and nonsignificantly associated with lesser left hemisphere bias in the panic disorder group.

Detection and quantification of complexed and free soluble human vascular endothelial growth factor receptor-1 (sVEGFR-1) by ELISA.

Vascular endothelial growth factor (VEGF) is an important factor for endothelial cell proliferation and a key regulator of blood vessel development in embryos and angiogenesis in adult tissues. Its biological activity is mediated by two receptor tyrosine kinases, VEGFR-1 (Flt-1) and VEGFR-2 (KDR). In contrast to VEGFR-2, a naturally occurring soluble form of the VEGFR-1 (sVEGFR-1) is produced by endothelial cells by differential splicing of the flt-1 gene, and it is a secreted gene product. In order to develop a specific enzyme-linked immunosorbent assay (ELISA) for the measurement of sVEGFR-1, we established five anti-human receptor antibodies and characterized them in detail. These antibodies recognize different epitopes located within the seven Ig-like domains of the extracellular receptor protein but have no neutralizing activity in ligand binding assays. Together with a polyclonal antiserum, a specific human sVEGFR-1 ELISA was developed using the mAb #190.11. The ELISA can detect human sVEGFR-1 with a minimum detection limit of 1 ng/ml. The ELISA does not show any cross-reactivity with other related soluble receptors. Using this assay, human sVEGFR-1 was measured in the supernatant of different VEGFR-1 expressing cell types. No sVEGFR-1 protein was detectable after heparin Sepharose treatment or size-exclusion filtration (< 30 kDa). The ELISA assay for sVEGFR-1 was also used to measure the amount of the soluble receptor in amniotic fluid samples of patients undergoing amniocentesis during the course of normal pregnancies. The concentration of the samples was in the range of 5-35 ng/ml. This ELISA could be useful powerful tool for investigations concerning the physiological function of the soluble receptor under normal and pathophysiological conditions.Furthermore, it may facilitate studies of the mechanisms of receptor production.

Surgical and medical management of patients with massive cerebellar infarctions: results of the German-Austrian Cerebellar Infarction Study.

Surgical intervention (ventricular drainage or decompressive craniotomy) may be necessary in patients with cerebellar infarction if mass effect develops. However, patient selection and timing of surgery remain controversial, and there are few data on clinical signs in the early course that are predictive for outcome. The clinical course and neuroradiological features of 84 patients (aged 22-78, mean 58.5 years) with massive cerebellar infarction confirmed by computed tomography were prospectively observed for 21 days after admission and at 3-month follow-up using a standardized protocol. Data were gathered from 1992 to 1996 in 17 centers. The patients were assigned to three treatment groups depending on the decision of the primary caretaker: 34 underwent craniotomy and evacuation, 14 received ventriculostomy, and 36 were treated medically. Treatment groups differed regarding the level of consciousness, signs of mass effect in computed tomography and signs of brainstem involvement. The overall risk for poor outcome depended on the level of consciousness after clinical deterioration (odds ratio = 2.8). Subgroup analysis of awake/drowsy or somnolent/stupor patients revealed no relationship to treatment. The vascular territory involved did not affect outcome. Surgical treatment for massive cerebellar infarctions was not found to be superior to medical treatment in awake/drowsy or somnolent/stupor patients. Half of all patients deteriorating to coma treated with ventricular drainage or decompressive craniotomy had a meaningful recovery. We were unable to compare surgical versus medical therapy in this subgroup due to lack of control group. This study supports the notion that the level of consciousness is the most powerful predictor of outcome, superior to any other clinical sign and treatment assignment. Deterioration of consciousness typically occurred between days 2 and 4, with a maximum on day 3.

[Gerontopsychiatric treatment in comparison between integrated management at a university and separated management at a district hospital. 1: Patient characteristics]. / Gerontopsychiatrische Behandlung im Vergleich zwischen integrierter Versorgung an einer Universität und separierter Versorgung an einem Landeskrankenhaus. Teil 1: Patientencharakteristik.

OBJECTIVE: We wanted to study differences between geriatric psychiatric patients and their management in an integrated (with other adult age groups) care in the University Psychiatric Hospital (PUK) compared to those in a separated (only according to age) care in the Psychiatric State Hospital (LKH), which together treat all psychiatric inpatients in Goettingen, Germany. METHOD: We performed standardized chart reviews of randomly selected groups of patients, who had been treated in the PUK (n = 151) and the LKH (n = 145) in the years 1991 and 1992. RESULTS: The LKH patients were significantly older (74.8 +/- 8.7 y versus 70.3 +/- 8.3 y), more often living alone and/or without children. 31.9% of them were living in a nursing home compared to 6.5% of the PUK patients. Psychic disorders had not shown up before old age in 55.7% of all cases. 50.4% of the patients were in a psychiatric hospital for the first time. The majority of the patients (65.6%) had not been investigated by a psychiatrist before admission. CONCLUSIONS: More socially handicapped patients were treated in the LKH. For most cases, the hospital treatment had been the first psychiatric treatment at all.

[Gerontopsychiatric treatment in comparison between integrated management at a university and separated management at a district hospital. 2: Diagnoses and treatment]. / Gerontopsychiatrische Behandlung im Vergleich zwischen integrierter Versorgung an einer Universität und separierter Versorgung an einem Landeskrankenhaus. Teil 2: Diagnosen und Behandlung.

OBJECTIVE: We wanted to study differences between geriatric psychiatric patients and their management in an integrated (with other adult age groups) care in the University Psychiatric Hospital (PUK) compared to those in a separated (only according to age) care in the Psychiatric State Hospital (LKH), which together treat all psychiatric inpatients in Goettingen, Germany. METHOD: We performed standardized chart reviews of randomly selected groups of patients, who had been treated in the PUK (n = 151) and the LKH (n = 145) in the years 1991 and 1992. RESULTS: Most patients of the LKH suffered from organic brain diseases/dementia (63.4%; PUK: 29.1%). In the PUK, depression was the most frequent diagnosis (57.6%; LKH: 21.1%). A part of about 25% of the patients showed neurological deficits. Specialised diagnostics were performed mostly in the PUK. Both institutions treated the wide majority of patients with CNS drugs. Antidementia drugs were given significantly more often in the LKH. About one third of the patients were released into changed living environments. CONCLUSIONS: Patients with further progressed dementias were treated mainly in the LKH. This has consequences for diagnostics, treatment duration and side effect rate.

Soluble VEGF receptors.

The three human VEGF receptors 1-3 mediate biological signals important for new blood vessel formation and lymphangiogenesis. Soluble VEGF receptors contain all the information necessary for high affinity ligand binding and have been used as experimental tools and regulators in several angiogenic in vitro and in vivo models. Recombinant receptor molecules can be used for specific inhibition of VEGF mediated signal transduction and for blocking tumor angiogenesis by limiting the amount of VEGF secreted from tumor cells or stroma cells. A naturally occurring soluble VEGFR-1 has been discovered in the supernatant from endothelial cells and at present appears to be the key regulator for the availability of VEGF secreted from different cells and tissues. The exact physiological role has not yet been demonstrated.

Soluble and cell surface ICAM-1 as markers for disease activity in multiple sclerosis.

OBJECTIVE: The intercellular adhesion molecule-1 (ICAM-1) is a member of the Ig supergene family. ICAM-1 is expressed on various cells like peripheral blood lymphocytes, endothelial cells or thymic cells and the cell surface form is supposed to be shed into a soluble form. The expression of ICAM-1 is induced by cytokines like Interleukin-1, TNF alpha or interferon gamma. The aim of the study was to investigate whether changes of cell surface and soluble ICAM-1 in the cerebrospinal fluid (CSF) and blood are indicative for disease activity in patients with multiple sclerosis (MS). MATERIAL AND METHODS: In all patients with relapsing-remitting MS (relapse: n=31, remission: n=11) and controls (n=13) the expression of cell surface ICAM-1 (c-ICAM-1) was determined by two colour flow cytometry. Soluble ICAM-1 (s-ICAM-1) was measured by ELISA. Follow-up examinations were done 3 months later. RESULTS: In 31 patients with a current relapse we found significantly decreased expression levels of c-ICAM-1 on leukocytes in CSF (P<0.001) and blood (P<0.10), when compared to those 11 individuals experiencing remission. In contrast we observed significantly (P<0.05) increased levels of s-ICAM-1 in CSF of patients with relapses. Comparing patients who had been in remission for more than 4 weeks (n=11) with remission lasting longer than 3 months (n=28) we detected stable c-ICAM-1 expression on CD3+ T cells in blood. CONCLUSION: Our results demonstrate for the first time that c-ICAM-1 on CD3+ T-cells in CSF and blood is an activity marker in MS.

Receptors of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in fetal and adult human kidney: localization and [125I]VEGF binding sites.

Vascular endothelial growth factor (VEGF) has an important function in renal vascular ontogenesis and is constitutively expressed in podocytes of the adult kidney. The ability of VEGF to be chemotactic for monocytes and to increase the activity of collagenase and plasminogen activator may have implications for renal development and renal disease. In humans, the cellular actions of VEGF depend on binding to two specific receptors: Flt-1 and KDR. The aims of this study were: (1) to localize VEGF receptor proteins in human renal ontogenesis; (2) to quantify VEGF binding in human fetal and adult kidney; and (3) to dissect the binding into its two known components: the KDR and Flt-1 receptors. The latter aim was achieved by competitive binding of VEGF and placenta growth factor-2, which only binds to Flt-1. Quantification of 125I-VEGF binding sites was performed by autoradiography and computerized densitometry. By double-label immunohistochemistry, VEGF receptor proteins were localized solely to endothelial cells of preglomerular vessels, glomeruli, and postglomerular vessels. In developing glomeruli, VEGF receptor protein appeared as soon as endothelial cells were positive for von Willebrand factor. Specific 125I-VEGF binding could be localized to renal arteries and veins, glomeruli, and the tubulointerstitial capillary network in different developmental stages. Affinity (Kd) of adult (aK) and fetal (fK) kidneys was: Kd: glomeruli 38.6 +/- 11.2 (aK, n = 5), 36.3 +/- 7.1 (fK, n = 5); cortical tubulointerstitium 19.4 +/- 2.6 (aK, n = 5), 11.6 +/- 7.0 (fK, n = 5) pmol. Placenta growth factor-2 displaced VEGF binding in all renal structures by approximately 60%. VEGF receptor proteins thus were found only in renal endothelial cells. A coexpression of both VEGF binding sites could be shown, with Flt-1 demonstrating the most abundant VEGF receptor binding sites in the kidney. These studies support the hypothesis of a function for VEGF in adult kidney that is independent of angiogenesis.

Stages and syndromes of neuroborreliosis.

To ascertain the varieties of neuroborreliosis, 330 patients were identified at the Departments of Neurology in Würzburg and Giessen from 1979 to 1994. Patients who fullfilled at least one of three strict case definitions based on clinical and laboratory criteria were included in the study. Ninety-one per cent of the patients had second-stage neuroborreliosis (duration of symptoms < or = 6 months). The most common syndrome was a painful spinal meningoradiculitis, alone (37%) or in combination with a cranial radiculitis (29%). Meningoradiculitis cranialis (9%), isolated meningitis (4%) and erythema chronica migrans-associated mono/polyneuritis (3%) were further stage II features. Central nervous system involvement occurred either as an acute meningomyelitis or meningomyeloradiculitis (5%) and meningoencephalitis or meningenocephaloradiculitis (4%). Less than 9% of the patients ran a chronic course (stage III) with a disease duration between 6 months and 9 years, either as acrodermatitis chronica atrophicans associated mono- or polyneuritis (2%) or a chronic progressive encephalomyelitis (6%). Cerebrovascular neuroborreliosis (1%) occurred in both stages; however, the primary nature of the course was a chronic one. Involvement of other organs except the skin was rare (joints 3%, heart 1%) but elevated hepatic enzymes were frequent. Our study demonstrates that neuroborreliosis has to be considered in the differential diagnosis of a wide variety of neurological conditions. Cerebrospinal fluid analysis and the search for specific intrathecal antibody production are important diagnostic procedures.