Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion

The effect of flow on the adhesion of polymorphonuclear leukocytes (PMNL) to vascular endothelium was investigated using a parallel plate chamber with a well-defined flow field. Washed PMNL were perfused over a monolayer of primary human umbilical vein endothelial cells (HUVEC) pretreated with formyl-methionyl-leucyl-phenylalanine (FMLP, 1 X 10(-7) mol/L) for five minutes. In other experiments HUVEC were pretreated with interleukin 1 (IL1,2 U/mL) for four hours. PMNL adhesion to stimulated and control HUVEC was measured over a physiologic range of wall shear stresses. PMNL adhesion to nylon-coated surface was also studied. At a wall shear stress of 0.98 dynes/cm2,283 +/- 37.3 PMNL/mm2 (mean +/- SEM) adhered to FMLP-treated HUVEC while 195 +/- 20.3 PMNL/mm2 adhered to control HUVEC. At 1.96 dynes/cm2, 68 +/- 14.1 PMNL/mm2 adhered to FMLP-treated HUVEC and 42 +/- 6.0 PMNL/mm2 adhered to control HUVEC. At 3.92 dynes/cm2, virtually no PMNL adherence was noted on either control or FMLP-treated HUVEC. On IL 1-treated HUVEC at 1.96 dynes/cm2, 371 +/- 25.8 PMNL/mm2 adhered while 28 +/- 2.9 PMNL/mm2 adhered to control HUVEC. PMNL adhesion to IL 1-treated and control HUVEC dropped to 10.2 +/- 3.8 and 6.8 +/- 3.5 PMNL/mm2, respectively, at 3.01 dynes/cm2. The effect of flow on PMNL adhesion appears to be an important factor in determining the outcome of the PMNL/HUVEC adhesive interaction under these experimental conditions.     

Interleukin-1 alpha upregulates tumor necrosis factor receptors expressed by a human bone marrow stromal cell strain: implications for cytokine redundancy and synergy

To explore the biochemical and physiologic basis of the overlapping effects of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF-alpha) on myeloid cytokine production, we have studied the dynamics of granulocyte colony-stimulating factor (G-CSF) and granulocyte-monocyte colony-stimulating factor (GM-CSF) production as well as IL-1 receptor and TNF receptor expression in a clonally derived bone marrow stromal cell strain (CDCL). IL-1 alpha and TNF alpha act in a synergistic manner to stimulate G-CSF and GM-CSF production by CDCL, resulting in an increase in CSF secretion that is 250-fold greater than that observed with either cytokine alone. This synergism in protein secretion is paralleled by synergistic increases the steady-state level of GM- and G-CSF mRNA, with supra-additive levels achieved by 24 hours. Coincident with this synergistic induction of myeloid CSFs, treatment of CDCL cells with IL-1 alpha induces a 300% increase in the expression of TNF receptors. IL-1 alpha induction of TNF receptors reaches a peak after 6 hours and gradually returns to baseline level by 24 hours. IL-1 alpha does not affect TNF receptor ligand binding affinity. A kinetic study comparing IL-1/TNF synergistic induction of growth factor secretion with IL-1 alpha induction of TNF receptors shows that these events occur in parallel. In contrast with the induction of TNF receptors by IL-1 alpha, treatment with TNF alpha has no effect on either the number of IL-1 receptors expressed by CDCL cells or IL-1 receptor ligand binding affinity. Brief treatment of IL-1 alpha/TNF alpha-stimulated CDCL cells with cycloheximide before receptor induction reduces the synergistic increase in growth factor mRNA by 40% to 60% compared with cells not treated with CHX. Taken together, these results raise the possibility that IL-1 alpha cross-induction of TNF receptors may contribute to the biochemical mechanisms underlying the synergistic stimulation of G-CSF and GM-CSF production by IL-1 alpha and TNF alpha.     

Zur Rechtmäßigkeit einer sachlich-rechnerischen Honorarberichtigung in Gestalt eines Vertikalvergleichs durch eine Kassenärztliche Vereinigung

Ohne Zusammenfassung     

A point mutation associated with a severe phenotype of neurofibromatosis 2

Neurofibromatosis 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas and other nonmalignant tumors of the brain, spinal cord, and peripheral nerves. Although the average age of onset of NF2 is 20 years, some individuals may become symptomatic in childhood. We studied 5 unrelated NF2 patients who became symptomatic before age 13. All 5 had multiple tumors in addition to vestibular schwannoma, and none had a positive family history. Sequence analysis of the NF2 gene revealed identical nonsense mutation of exon 6 in 3 patients. Because this mutation destroys a restriction site, genomic DNA from the 2 other children was directly tested for this change and identical alterations were detected. Although the work of our laboratory and others has not, in general, detected identical mutations in unrelated patients, this mutation seems to occur particularly frequently in the pediatric population and thus may be associated with an especially severe phenotype. Restriction analysis in children with NF2 may be a cost effective way of identifying their mutation. Further work is needed to characterize the effects of this change on the NF2 protein product and its relationship to this severe phenotype.     

Integrierte Versorgung – Voraussetzungen für den Abzug der sog. Anschubfinanzierung von der Gesamtvergütung durch eine Krankenkasse

Abstrakt 1. Für die Berechtigung der Krankenkasse zum Einbehalt der Anschubfinanzierung kommt es auf bereits geschlossene IV-Vertr?ge an. 2. Apotheken geh?ren nicht zu den nach § 140b SGB V zum Vertragsabschluss berechtigten Leistungserbringern. 3. Zum Sinn und Zweck einer Integrierten Versorgung. (Leits?tze des Bearbeiters)     

Multidisciplinary prediction of seizure relief from cortical resection surgery

Preoperative variables from a full range of medical specialties were used to predict degree of seizure relief from cortical resection surgery as treatment for epilepsy in 100 patients. General, seizure history, electroencephalographic (EEG), radiological, surgical, and psychological/neuropsychological data were considered. The patients were divided into one large predictive group (n = 75) and a smaller independent cross-validation sample (n = 25). Eight predictive variables emerged: single EEG focus; anterior-midtemporal lobe discharges; discharges only from the side of surgery; rate of occurrence of discharges in surgical area; Wechsler Adult Intelligence Scale Digit Symbol subtest; Marching Test, preferred hand, time; Minnesota Multiphasic Personality Inventory (MMPI) Hysteria scale score; and MMPI Paranoia scale score. By use of multivariate procedures, increased predictability of surgical outcome was obtained not only with the predictive group but with the independent cross-validation sample. The results demonstrate that predictions of seizure relief from epilepsy surgery can be made with 80% accuracy using multiple, rather than single, predictors.     

Abrechnung der Nrn. 17 und 19 EBM nebeneinander

Abstrakt Im Einzelfall kann im Rahmen einer Behandlung am selben Tag der Ansatz sowohl der Nr. 17 EBM als auch der Nr. 19 gerechtfertigt sein. (Leitsatz des Bearbeiters)