Effects of the depth of anesthesia on distortion product otoacoustic emissions

To analyze the effects of the depth of anesthesia on inner ear function measured with distortion product otoacoustic emissions (DPOAEs) at 2f ₁ ? f ₂. Thirty patients who underwent tonsillectomy under general anesthesia (GA) were included. Patients were assigned randomly to one of two groups: group 1 (n = 15) received propofol, group 2 (n = 15) sevoflurane as anesthetic agent. The sedation level was assessed by the bispectral index system. DPOAE measurements were performed before premedication (T ₁), 5 min after premedication (T ₂), 3 min after induction of general anesthesia (T ₃) and every 10 min (T ₄, T ₅) thereafter until the end of surgery at about 23 min post-anesthetic induction, while sedation levels were obtained starting at the beginning until the end of anesthesia. After premedication, both blood oxygen saturation and heart rate decreased. Following induction of anesthesia systolic and diastolic blood pressure decreased, while, as expected, the level of sedation increased. Analyzing the propofol and sevoflurane group separately, both groups showed comparable overall courses of DPOAE levels at higher frequencies (2.8 kHz p = 0.310, 4 kHz p = 0.193, 6 kHz p = 0.269, 8 kHz p = 0.223) and no changes of DPOAE levels compared with baseline values were observed. At T₅ the 1 kHz DPOAE level increased in the propofol group and slightly decreased in the sevoflurane group (p < 0.001). While the 1.4 kHz DPOAE level in the propofol group did not change over time the 1.4 kHz DPOAE level decreased in the sevoflurane group (baseline to T ₄ p = 0.045; Baseline to T ₅ p = 0.004). While overall there were different courses between these two groups in the 2 kHz DPOAE level, in the post hoc analysis only a tendency in the change from baseline to T ₄ could be observed (p = 0.082). These results indicate that while the amplitudes of certain DPOAEs were influenced by GA, the depth of anesthesia had no effect on this measure of cochlear function in clinical routine. Therefore, DPOAE measurements in sedation and during GA are useful but the effect of anesthetic agents on DPOAE levels needs to be taken into account when analyzing the test.     

Follow up of children after antenatal treatment for alloimmune thrombocytopenia

OBJECTIVE: To evaluate the long-term follow-up of surviving offspring after antenatal treatment for fetal or neonatal alloimmune thrombocytopenia (FNAIT). PATIENTS: Fifty children at risk of FNAIT were antenatally treated with maternal intravenous immunoglobulins (IVIG) (n=11), IVIG with intrauterine platelet transfusions (IUPT) (n=26) or IUPT alone (n=9). In four cases (n=4), only fetal blood sampling (FBS) was performed. One child died in the neonatal period and one was lost to follow up. METHODS: The remaining 48 children, aged 1.3-11.6 years (median 5.1 years), were given both general and neurological examinations and assessed on their development and susceptibility for infections or atopic constitution. In addition, immunoglobulin levels were measured in 17 infants, aged 5 years and older. RESULTS: Intracranial hemorrhage (ICH) was not observed. The general health and neurodevelopmental outcome in the children was comparable to a normal Dutch population. Children not exposed to maternal IVIG treatment had significantly more infections and hearing problems than children exposed to IVIG treatment or the normal population. Immunoglobulin G, A and M levels were within the normal range, independent of treatment and severity of FNAIT. A high IgE level was more frequently seen in children exposed to IVIG, but did not result in clinical consequences such as allergy or atopy. CONCLUSIONS: Antenatal treatment of children for FNAIT did not affect general health or neurodevelopmental outcome. In particular, exposure to IVIG in utero showed no adverse effect on the clinical outcome of these children.     

Proliferative activity of leukaemic blasts and cytosine arabinoside pharmacodynamics are associated with cytogenetically defined prognostic subgroups in acute myeloid leukaemia

The biological mechanisms responsible for the association of specific karyotypes with prognosis in acute myeloid leukaemia (AML) remain largely unclear. A prospective study was performed to evaluate how far cytogenetically defined prognostic subgroups of AML differ in their proliferative activity as a potential mechanism for differential sensitivities to S-phase-specific induction chemotherapy comprising cytosine arabinoside (AraC). One hundred and eighty-seven patients with de novo AML were included in the study; 25 patients with a favourable [inv(16), t(8;21), t(15;17)] karyotype, 99 with a normal karyotype, 29 with an unfavourable karyotype (-5, 5q-, -7, 7q-, complex aberrations) and 34 with cytogenetic aberrations of unknown prognostic significance (all others). The favourable group demonstrated the highest ex vivo proliferative activity (PA) (3.41 pmol/105 cells), significantly (P = 0.02) exceeding the unfavourable group with the lowest PA (0.72) and the group with a normal karyotype (1.06) or with karyotype of unknown significance (1.05) that both demonstrated an intermediate PA. Samples with a high PA (> median of the whole group) were more likely to produce interleukin 3, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF) (56%, 43% and 50%) than cells with a low PA (33%, 36% and 36%; n.s.). The effect of priming by exogenous GM-CSF or G-CSF was significantly more pronounced in samples with a low PA than in rapidly proliferating samples (P < 0.01). For the whole group, a high PA was closely associated with an increased incorporation of AraC triphosphate (AraCTP) into the DNA (P < 0.0001). Clinically, a high PA was associated with a better complete remission (CR) rate in the normal (95% versus 62%) and the unfavourable group (75% versus 33%). The significant differences in proliferative activity between cytogenetic subgroups of AML are associated with increased cytosine arabinoside pharmacodynamics and constitute one potential mechanism for the different response of cytogenetic subgroups to AraC-based induction therapy.     

Deleted in liver cancer 1 controls cell migration through a Dia1-dependent signaling pathway

Deleted in liver cancer (DLC) 1 and 2 are Rho GTPase-activating proteins that are frequently down-regulated in various types of cancer. Ectopic expression in carcinoma cell lines lacking these proteins has been shown to inhibit cell migration and invasion. However, whether the loss of DLC1 or DLC2 is the cause of aberrant Rho signaling in transformed cells has not been investigated. Here, we have down-regulated DLC1 and DLC2 expression in breast cancer cells using a RNA interference approach. Silencing of DLC1 led to the stabilization of stress fibers and focal adhesions and enhanced cell motility in wound-healing as well as chemotactic Transwell assays. We provide evidence that enhanced migration of cells lacking DLC1 is dependent on the Rho effector protein Dia1 but does not require the activity of Rho kinase. By contrast, DLC2 knockdown failed to affect the migratory behavior of cells, suggesting that the two proteins have distinct functions. This is most likely due to their differential subcellular localizations, with DLC1 found in focal adhesions and DLC2 being mainly cytosolic. Collectively, our data show that DLC1 is critically involved in the control of Rho signaling and actin cytoskeleton remodeling and that its cellular loss is sufficient for the acquisition of a more migratory phenotype of breast cancer cells.     

Morphologie

Ohne Zusammenfassung     

The electroencephalographic sleep pattern in schizophrenic patients treated with clozapine or classical antipsychotic drugs

The effects of antipsychotic agents on sleep were tested by examining the nocturnal electroencephalographic recordings of 14 drug-naïve schizophrenic patients and comparing these with recordings from 12 patients treated with clozapine and 10 treated with classical neuroleptics (haloperidol: n=7; flupentixol: n=3). In both of the treated groups, sleep continuity measures and rapid eye movement (REM) density were significantly higher than in the drug-naïve group. Clozapine-treated patients showed significantly more stage two sleep, more stable non-REM sleep (stages two, three and four) and less stage one than patients treated with haloperidol or flupentixol. Clozapine had no effect on the amount of REM sleep. Although mean REM latency was almost twice as long in the clozapine compared with the other two groups, this difference was not statistically significant. The present study suggests considerable differences between the influence of typical and atypical antipsychotic agents on sleep. However, the results of this cross-sectional study should be confirmed using a longitudinal intraindividual approach.     

Acute and long-lasting changes in extracellular-matrix chondroitin-sulphate proteoglycans induced by injection of chondroitinase ABC in the adult rat brain

Lattice-like perineuronal accumulations of extracellular-matrix proteoglycans have been shown to develop during postnatal maturation and to persist throughout life as perineuronal nets (PNs) in many brain regions. However, the dynamics of their reorganization in adults are as yet unknown. The aim of the present study was to examine the capability of PNs for reconstitution after experimental destruction and to search for possible consequences of extracellular-matrix degradation for neurons and glial cells. The changes were induced by single intracortical injections of Proteus vulgaris chondroitinase ABC and studied after postinjection periods of 1 day to 5 months. The N-acetylgalactosamine-binding Wisteria floribunda agglutinin (WFA), an antibody against chondroitin-sulphate proteoglycans, three antibodies recognizing initial chondroitin or chondroitin-sulphate moieties (’stubs’) of proteoglycan core proteins, an antibody against the hyaluronan-binding protein component of versican, and biotinylated hyaluronectin, which binds to hyaluronan, were used as cytochemical markers. One day postinjection, the WFA-binding sites and hyaluronan were shown to be almost completely removed within a circumscribed digestion zone. The staining of different core-protein components revealed only fragments of PNs. These changes were found to be partly compensated 4 weeks after injection of chondroitinase ABC. After 8 and 12 weeks postinjection, the cytochemical and structural characteristics as well as the area-specific distribution patterns of PNs were progressively reconstituted. At 5 months postinjection, they could not be distinguished from those in untreated tissue. In contrast to such transient changes, a diffuse chondroitin-sulphate proteoglycan immunoreactivity persisted in the neuropil. Loss of neurons or alterations of their structure as well as reactions of glial cells were not observed. We conclude from this study that PNs, enzymatically destroyed in the adult rat brain, can be completely reconstituted, but the restoration of their extracellular-matrix components needs several months. Received: 16 December 1997 / Accepted: 17 February 1998