Darbepoetin alfa protects podocytes from apoptosis in vitro and in vivo.

Detachment or apoptosis of podocytes leads to proteinuria and glomerulosclerosis. There are no current interventions for diabetic or non-diabetic glomerular diseases specifically preventing podocyte apoptosis. Binding of erythropoiesis stimulating proteins (ESPs) to receptors on non-hematopoietic cells has been shown to have anti-apoptotic effects in vitro, in vivo, and in preliminary human studies. Recently, erythropoietin receptors were identified on podocytes; therefore, we tested effects of darbepoetin alfa in preventing podocyte apoptosis. Cultured immortalized mouse podocytes were treated with low-dose ultraviolet-C (uv-C) irradiation to induce apoptosis in the absence or presence of darbepoetin alfa. Apoptosis was quantified by Hoechst staining and by caspase 3 cleavage assessed by Western blots. Pretreatment with darbepoetin alfa significantly reduced podocyte apoptosis with this effect involving intact Janus family protein kinase-2 (JAK2) and AKT signaling pathways. Additionally, darbepoetin alfa was found protective against transforming growth factor-beta1 but not puromycin aminonucleoside induced apoptosis. Mice with anti-glomerular antibody induced glomerulonephritis had significantly less proteinuria, glomerulosclerosis, and podocyte apoptosis when treated with darbepoetin alfa. Our studies show that treatment of progressive renal diseases characterized by podocyte apoptosis with ESPs may be beneficial in slowing progression of chronic kidney disease.

The chimpanzee and cynomolgus monkey erythrocyte immune adherence receptors are encoded by CR1-like genes.

The human erythrocyte immune adherence (IA) receptor is the Mr 220,000 type one complement receptor, or CR1. Nonhuman primate IA receptors are comprised of a family of smaller erythrocyte complement receptors (E-CRs) of unknown origin. Recently, the Mr 65,000 baboon E-CR was identified as a glycophosphatidylinositol (GPI)-linked protein encoded by a partially duplicated CR1 gene termed CR1-like. The purpose of this study was to determine the genetic origin of the Mr 75,000 chimpanzee E-CR. Two previously identified cDNAs, an alternative splice product of CR1 termed CR1a and a chimpanzee form of CR1-like, were synthesized and amplified from chimpanzee bone marrow RNA, and transiently expressed in COS-7 cells. By SDS-PAGE, the CR1a protein had a relative mobility slightly greater than chimpanzee E-CR, whereas that of the CR1-like protein was slightly less. Affinity chromatography demonstrated that little chimpanzee CR1a bound to human C3i linked to activated thiol-Sepharose (C3i-ATS), while over 50% of both chimpanzee CR1-like and chimpanzee E-CR bound to C3i-ATS. Treatment with phosphatidylinositol-specific phospholipase C (PIPLC) to assess GPI linkage released E-CR from chimpanzee erythrocytes, and E-CR from cynomolgus monkey erythrocytes. Based on size, ligand-binding specificity, and PIPLC sensitivity, we conclude that the chimpanzee E-CR is encoded by the CR1-like gene. Furthermore, based on PIPLC sensitivity, the cynomolgus monkey E-CR is also likely encoded by a CR1-like sequence. Thus, CR1-like, which is a genetic element of unknown significance in humans, is the gene that encodes the erythrocyte IA receptor of many nonhuman primates.

Referring physician satisfaction: toward a better understanding of hospital referrals.

Customer satisfaction literature has contributed significantly to the development of marketing strategies in the health-care arena. The research has led to the development of hospital-driven relationship marketing programs. This study examines the inclusion of referring physicians as partners in the hospital's relationship marketing program. In exploring this relationship, medical and hospital facility characteristics that referring physicians find important in making patient referrals to specialty care hospitals are identified and analyzed. The results lead to the development of strategic initiatives which hospital marketers should consider when developing relationship marketing programs designed to satisfy their referring physicians.

The baboon erythrocyte complement receptor is a glycophosphatidylinositol-linked protein encoded by a homologue of the human CR1-like genetic element.

The human erythrocyte CA receptor (E-CR) is the type 1 complement receptor (CR1), the most common form of which is a 220,000 Mr integral membrane glycoprotein composed of 30 short consensus repeats (SCRs). The E-CR of many nonhuman primates is a smaller receptor of unknown genetic origin. Recently, we identified a chimp cDNA, termed CR1b, which represented transcription of a homologue of the human genetic element, CR1-like. The purpose of this study was to identify CR1b in the baboon and, if present, determine whether it encodes the 65,000 Mr baboon E-CR. Baboon bone marrow cDNA was amplified by PCR using primers specific for the signal peptide-encoding region of human CR1 and the 3' region of chimp CR1b. This amplification yielded a CR1b sequence predicted to encode seven SCRs followed by a hydrophobic region, with an N terminus homologous to the N terminus of baboon E-CR. Expression of baboon CR1b yielded a membrane protein that reacted with an anti-CR1 mAb, was identical in size to baboon E-CR, and, like baboon E-CR, could bind baboon C3 linked to activated thiol-Sepharose (C3i-ATS), but not human C3i-ATS. Phosphatidylinositol-specific phospholipase C (PIPLC) released CR1b from Chinese hamster ovary cells and E-CR from baboon erythrocytes, demonstrating that both of these proteins are glycophosphatidylinositol linked to the membrane. Thus, the data indicate that baboon CR1b, a homologue of the human CR1-like genetic element, encodes a glycophosphatidylinositol-linked protein that is the baboon E-CR.

EEG mapping--a new way of monitoring in epilepsy.

A method for comparison of EEG mapping findings on the basis of numeric data, i.e. the numeric power values measured at the electrode sites for each frequency band, is described. Examples for the clinical use of comparison studies in epileptic patients are given. The problems regarding methodological issues are discussed.

Role of long-term EEG monitoring in diagnosis and treatment of epilepsy.

The value of long-term EEG recordings for diagnosis and differential diagnosis of epilepsy is described. It is emphasized that long-term EEF monitoring increases the scope of EEG techniques and improves the diagnostic value of standard EEG recordings providing up to 90% positive diagnostic information. In particular, the value of ambulatory cassette recording is stressed. Allowing quantification of epileptic activity recorded in real-life situation, useful information not available by means of standard EEG recordings can be obtained. Recording and scoring all-night sleep, it enables studying abnormalities of sleep patterns. In addition the value of long-term EEG recordings in therapy and control of epileptic patients is pointed out and discussed.

EEG mapping in middle aged normal volunteers: the impact of cerebrovascular risk factors.

The impact of major risk factors for stroke on EEG mapping and routine EEG findings was evaluated in volunteers with no clinical signs of cerebrovascular or other neuropsychiatric disease. Focal changes were seen in 22 subjects (30%) by means of EEG mapping, but in only 12 cases (16%) when routine-EEG was used (p < .05). 4/35 (11%) volunteers without RF had focal changes while this was seen in 18/39 (46%) subjects in whom risk factors (RF) were found (p < .01). An association was seen between the presence of EEG foci and number of RF. 59% of subjects with 2 or 3 RF had focal abnormalities as opposed to 36% of those with 1 RF and 11% of RF free individuals (p < .05). The findings could be confirmed by averaging the EEG data according to the different number of RF revealing statistically significant differences between each of the 3 groups. Using routine EEG alone no significant correlation to the presence or number of RF was found. Our data demonstrate EEG abnormalities in a considerable portion of normal middle aged individuals which in part may be attributed to the presence of RF.

[A comparison of EEG mapping with and without visual artefact control in focal cerebral lesions]. / Vergleich des EEG-Mapping mit und ohne visuelle Artefakt-Kontrolle bei fokalen zerebralen Läsionen.

In 163 patients with focal cerebral lesions, 43 of them with completed stroke, 43 patients with TIA, 33 patients with ICH and 29 patients with malignant and 15 patients with benign tumors EEG mapping and CT was performed. The results of EEG mapping obtained using automated artifact detection were compared to those achieved by means of visual control of raw EEG. Furthermore the impact of long (850 +/- 250s) or short (32s) analysis time was studied. Eliminating artifacts by means of visual control of raw EEG significantly more positive results were obtained than using automated artifact detection. That was found in patients with as well as in patients without lesions in CT. In relation to etiology a significant difference was found only in cerebrovascular diseases but not in the other patients-groups. Corresponding results were found in 75% of the patients. The visual control provided additional lateralization especially in patients with CS (37%) and TIA (26%). A longer duration of analysed EEG epochs did not increase the number of focal changes in EEG mapping.

[The value of EEG mapping in intracerebral hematomas]. / Wert des EEG-Mapping bei intrazerebralen Hämatomen.

33 patients with intracerebral hemorrhage were studied and the findings of EEG mapping, routine EEG and CT were compared. It could be shown, that the EEG mapping revealed in 6 patients additional focal changes corresponding with the clinical signs compared to conventional EEG. Identical results of EEG mapping and CT were found in 27 patients. In 5 patients the focal changes were localised contralateral to the hyperdense lesion in CT, and in 1 patient the EEG mapping failed to show any lateralisation. A negative intercorrelation between the size of the hematoma and the frequency, which revealed the focal signs in EEG mapping, could be shown.

The EEG mapping in the evaluation of patients with late onset epilepsy.

In 62 patients with late onset epilepsy the findings of EEG mapping routine EEG and CT were compared. Forty four patients had generalized, 18 partial seizures. In 39 patients (63%) EEG mapping revealed focal changes but only in 24 patients (39%) using routine EEG alone. Thus the EEG mapping showed focal abnormalities significantly more often and this could be demonstrated in the separated groups of patients with generalized or partial seizures as well. Lesions in CT occurred in 39 patients (63%). The focal abnormalities in EEG mapping were significantly related to the lesions in CT. Moreover focal changes corresponding to CT lesions were obtained by means of EEG mapping in 32 patients (82%) but only in 20 patients (51%) using routine EEG and in that way the EEG mapping could indicate focal lesions in CT significantly more often than routine EEG. Regarding etiology this was especially seen in the group with vascular origin of epilepsy.

The value of EEG-mapping in focal cerebral lesions.

In 148 patients with focal cerebral lesions the findings of EEG mapping, routine EEG and CT were compared. Regarding etiology 43 patients suffered from completed stroke (CS), 43 patients from transient ischemic attack (TIA), 33 patients had an intracerebral hemorrhage (ICH) and 29 an hemispheric tumor. In 37 patients with CS (86%) and 27 patients with TIA (63%) the EEG mapping revealed focal changes, but only in 28 patients with CS (65%) and in 11 patients (26%) with TIA using routine EEG alone. Thus the EEG mapping showed focal abnormalities significantly more often. In the remaining patient groups no significant difference in the results of EEG mapping or routine EEG could be demonstrated. Focal abnormalities corresponding to focal lesions seen in CT were obtained by means of EEG mapping in 27 patients (90%) with CS and 10 patients (77%) with TIA, but only in 17 patients (57%) with CS and 4 patients (31%) with TIA using routine EEG and in that way the EEG mapping could indicate focal lesions in CT significantly more often than routine EEG. In the remaining patient groups no significant difference in the number of focal changes corresponding to lesions in CT could be seen.

[The place of EEG mapping in cerebral ischemia]. / Die Stellung des EEG-Mapping bei zerebralen Ischämien.

70 patients with Completed stroke were studied and the findings of routine EEG, EEG mapping and CT were compared. It could be shown, that the EEG mapping revealed significantly more often focal changes corresponding with the clinical signs (83%) than the routine EEG (57%). Hypodense lesions in CT were seen in 54 patients. Identical results of EEG mapping and CT were found in 50 patients, EEG mapping and routine EEG were identical in 46 patients. The EEG mapping provided additional lateralisation in 12 patients with negative CT findings and in 21 patients with negative routine EEG. In patients with hypodense lesions in CT the EEG mapping revealed significantly more often focal changes (85%) than the routine EEG (59)%).

Topographic EEG brain mapping in cerebrovascular disease and dementia.

1. The results of brain mapping had been studied in 27 patients with different stages of ischemic stroke and in 20 patients with dementia, ten of SDAT and ten of vascular type. 2. It has been shown that in ischemic stroke the mapping correlates better with the severity of clinical symptoms than with anatomical and hemodynamic imaging methods. For the differentiation of SDAT and VD the mapping showed a clear cut possibility of differentiation.

[EEG changes in early summer meningoencephalitis]. / EEG-Veränderungen bei Frühsommermeningoenzephalitis (FSME).

The nature and extent of EEG changes in 114 patients with tick-borne encephalitis were reported. The diagnosis was confirmed by the clinical picture, as well as the pathological increase in cells in the liquor and serologically by positive Ig-M titres. EEG findings were compared in patients with or without involvement of the brain. The EEG revealed pathological results in 76 patients, whereby the dominant pathological change was frequently occurring synchronous bursts of generalized slow bilateral waves. 12 patients with involvement of the brain all showed pathological EEG changes, a much higher rate than in the remaining patients and these findings were also more marked. However, 64 patients with clinical evidence of meningitic involvement showed pathological EEG changes, too.

[EEG changes in senile dementia of the Alzheimer type]. / EEG-Veränderungen bei seniler Demenz vom Alzheimer Typ.

Character and extent of changes in EEG in 45 patients with senile dementia of Alzheimer type (SDAT) were reported and the EEG-findings of patients with moderate (18) or severe (27) dementia were compared. The EEG-findings in these patients were compared with a group of 82 patients with multi-infarct dementia (MID). The EEG showed pathological results in 37 patients with predominating general changes (59%). In patients with severe dementia significantly more pathological results especially a significantly slower basic rhythm could be found. The degree of the cerebral atrophy verified by CT did not correspond with character and extent of the changes in EEG. The comparison between patients with SDAT and 82 patients with MID, revealed a significantly more frequent occurrence of unilateral slowing of the basic rhythm but a less frequent occurrence of focal changes. However, there was no significant difference in the number of normal and pathological EEG. The comparison between patients with SDAT and patients with MID without neurological deficit failed to show a significant difference in the number of normal and pathological EEG as well. It could be shown that in patients with severe dementia the EEG revealed significantly more pathological results as well as a significantly slower basic rhythm. However, the EEG could not differentiate between SDAT and MID.

[Clinical assessment and therapy of barbiturate poisoning (based on 2 case reports)]. / Klinische Beurteilung und Therapie von Barbituratvergiftungen (an Hand von zwei Fallberichten).

The clinical features, complications and course of barbiturate poisoning are described and illustrated by two case histories in order to recommend therapeutic guidelines on the basis of practical experience. For the intensive care physician it is essential to get information on the composition of barbiturate-containing drugs as rapidly as possible in order to determine the correct therapeutic management. A table is presented of the components of the most commonly used barbiturates.

[EEG studies in bruxism with headache patients]. / EEG-Untersuchungen bei Bruxismuspatienten mit Kopfschmerzen.

EEG-investigations before and after long-term-treatment with occlusal-splints were carried out in 36 bruxism patients suffering from unilateral headache. The results of the latter group were compared to those of 41 patients with classical migraine and to those of a healthy control-group. 20 (56%) of our patients showed pathological EEG-pattern in which focal abnormalities (39%) were dominating. After a long-term-treatment, mentioned before, there was a significant decrease of pathological EEG-pattern combined with a distinct improvement of all clinical symptoms. In patients with classical migraine a higher number of pathological EEG-recordings were seen during attack as well as during interval. Comparing the EEG-findings of bruxism after treatment to those of the healthy controls, no significant differences were found anymore.

[EEG changes in cerebrovascular ischemia as affected by cardiac arrhythmias]. / EEG-Veränderungen bei zerebrovaskulären ischämischen Erkrankungen unter dem Einfluss von Rhythmusstörungen des Herzens.

124 patients with cerebrovascular ischemic disease were studied, 67 of them with irreversible neurological deficits, and the EEG-findings of patients with (50) or without cardiac arrhythmia (74) were compared. Moreover, the EEG-diagnoses of these patients were compared with 40 controls without cerebrovascular ischemic disease. Patients with irreversible neurological deficit had significantly more often cardiac dysrhythmia (51%) than patients with reversible neurological symptoms (28%). In patients with reversible neurological symptoms and in the control group no difference between patients with or without disturbance of the heart rhythm could be found. But in patients with irreversible neurological deficit in presence of cardiac dysrhythmia significantly more pathological EEG-findings could be found with significantly more pronounced EEG changes especially in presence of atrial fibrillation.

[EEG changes in symptomatic headache caused by bruxism]. / EEG-Veränderungen bei symptomatischem Kopfschmerz durch Bruxismus.

EEG recordings were carried out on 36 patients with the verified diagnosis of bruxism and unilateral headache. Occlusal splints were applied in the long-term management of these patients. Initial EEG recordings showed pathological changes in 56% of the patients. The EEG recordings were repeated two and six weeks later in these patients and following improvement in the clinical symptomatology pathological EEG patterns were detected in only 22% of all cases. This decrease is of statistical significance.