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R Neugebauer

Publications and source records attributed to R Neugebauer.

At least 19 recordsLinked to original sources

Synaptic targeting of N-methyl-D-aspartate receptor splice variants is regulated differentially by receptor activity.

The formation of postsynaptic clusters of various ligand-gated ion channels is regulated by receptor activity. Here we describe the developmental- and activity-dependent modification of N-methyl-D-aspartate (NMDA) receptor clustering in spinal cord neurons in vitro detected by immunofluorescence analysis using subunit and splice variant specific antibodies. NMDA receptors form synaptic and extrasynaptic clusters with sequential changes in subunit composition during in vitro development. During the first week of in vitro culture, a NR1 splice variant containing the C2-carboxy terminus and lacking the N1-cassette and the NR2B subunit are the prevailing components of receptor clusters at synaptic and extrasynaptic sites. After 3 weeks in culture (days in vitro [DIV] 22), the numbers of postsynaptic receptor clusters with N1-containing NR1 splice variants and NR2A subunits are upregulated. At DIV22, C2-specific clusters are abundant and are predominantly localized at postsynaptic sites, whereas the total number of C2'-clusters in dendrites is much lower and these clusters are localized mostly extrasynaptically. However, upon chronic inhibition of NMDA receptor activity in DIV8 and DIV22 cultures with MK801, the number of postsynaptic NR1-C2' subunit clusters is strongly upregulated. In contrast, numbers of NR1-C2 clusters are only modestly increased in DIV8 and not changed in DIV22 cultures upon MK801 treatment, suggesting a specific role of NR1 carboxy-terminal sequences in the activity-dependent synaptic targeting of NMDA receptor clusters of spinal cord neurons.

Alternative Splicing↗

[A comparative study of unstable per- and intertrochanteric femoral fractures treated with dynamic hip screw (DHS) and trochanteric butt-press plate vs. proximal femoral nail (PFN)].

The aim of the present paper is to compare the results obtained using two osteosynthesis systems developed for the surgical treatment of unstable fractures of the trochanteric region of the femur: the proximal femoral nail (PFN) and the dynamic hip screw (DHS) with trochanteric butt-press plate (TBPP). From December 1997 to November 2000, 173 patients with instable trochanteric fractures (type 31 A-2 and A-3 according to the AO-classification) had osteosynthesis by PFN (n = 122) or DHS/TBPP (n = 51). The average patient age was 74 years (range 27 to 98). No significant differences between the two study groups were observed with regard to age, sex, and rate of fracture types. At an average follow-up of 17 months the radiological and clinical outcome according to the score of "Merle d'Aubigné" was analysed in 61 % of all patients. All fractures were healed with no difference in functional outcome between the two groups. In the case of PFN 17.2 % revisions were necessary and in the case of DHS with TBPP 21.6 %. A shorter operation time (43 vs. 61 min) and a considerable shorter in-patient stay (20 vs. 24 days) were common with PFN. Full-weight-bearing immediately after the osteosynthesis was possible for 98 % of the PFN patients and 81 % of the DHS/TBPP patients. The DHS/TBPP osteosynthesis in instable trochanteric fractures is associated with a higher incidence of complications. Therefore we recommend to treat instable fractures of the trochanteric region with the PFN.

Adult↗

[Therapy of unstable sacrum fractures in pelvic ring fractures with dorsal sacrum distraction osteosynthesis].

Unstable pelvic ring injuries AO type C ("vertical shear") with a fractured sacrum are treated operatively in less than 50% of the cases (DGU pelvis study group). Furthermore, only 12% of these ORIF involve the sacrum bone itself. No specific technique has gained wide acceptance in treating transsacral instability. In accordance with earlier publications (Käch, Josten) suggesting an internal fixator, we developed the dorsal sacrum fracture distantly anchored ORIF (DSDO). This procedure closes the dorsal pelvic ring by joining the two dorsal iliac crests (fixed-angle screws inserted in the posterior superior iliac spine) and additionally anchors in a lumbar pedicle. Thus, a three-dimensional reduction and stable fixation device with optional local nerve decompression and even plating possibility is achieved. Between January 1996 and July 2001, 35 unstable sacrum disruptions were treated with DSDO in 180 patients operated for pelvic trauma. This allowed immediate mobilization in all cases. The radiologic follow-up examination ( n=20) revealed a solid union in all patients. Complications focused on management of the soft tissue degloving injury (Morel-Lavalleé lesion), which needs special attention.

Adolescent↗

[Special considerations in therapy of injuries of the cervical spine in ankylosing spondylitis (Bechterew disease)].

Cervical spine changed by Bechterew's disease is severely endangered with any increased load. Even decent trauma is enough to produce a fracture with affection of spinal cord. Because of little knowledge in these special items, late diagnosis of overlooked injury is not rare, especially in two-level injuries. Neurolesions following secondary fracture dislocations may occur ("fatal pause"). From january 1990 to february 2000 12 patients underwent surgery (dorsoventral stabilisation, ventral stabilisation, laminectomy). Diagnostic procedures, levels of injury, pre- and postoperative neurostatus (following Frankel's score), operative technique, typical complications and follow-up (Ø 17.8 months) were analyzed and compared with the literature. 11 patients showed preoperative neurodeficits. They were better in five cases and disappeared at all in another five cases after surgery (83% positive neurological outcome). There was no increase of neurology failure. Two patients died (ARDS and cerebral ischemia with destruction of vertebral arteries). One patient had to be reoperated because of implant dislocation. MRI is obvious in diagnostic for these lesions. There is also an absolute need for total (both clinical and radiological) examination of the whole spinal column, because there is often injury of more than one level (three times in our study). Therapy should be operative (dorsoventral stabilisation, in certain cases only anterior procedure or laminectomy). Late diagnosis and therapy with secondary worsening after fracture dislocation is not rare because of "overlooked injury". There were four patients, that would not have suffered cervical spine fracture (minimal injury force) without Bechterew's changes. There is often pulmonary failure through limitation of thoracic movement and cerebral ischemia following rupture of vertebral arteries as typical complications. Mortality (2 cases; 16%) in our collective is less than literature's medium rates (35-57%).

Adult↗

Anxiety disorders following miscarriage.

BACKGROUND: Several previous studies have established that miscarriage is a risk factor for depressive symptoms and disorder. By contrast, research on miscarriage as a possible risk factor for anxiety symptoms is inconclusive, and for anxiety disorders, sparse and uninformative. The current study examines the incidence of and relative risk for 3 DSM-III anxiety disorders (obsessive-compulsive disorder [OCD], panic disorder, and phobic disorders) within the 6 months following miscarriage. Adequate diagnostic data on other anxiety disorders were not available. METHOD: Using a cohort design, we tested whether women who miscarry are at increased risk for a first or recurrent episode of an anxiety disorder in the 6 months following loss. The miscarriage cohort consisted of women attending a medical center for spontaneous abortion (N = 229); the comparison group was a population-based cohort of women drawn from the community (N = 230). RESULTS: Among miscarrying women, 3.5% experienced a recurrent episode of OCD, compared with 0.4% of community women (relative risk [RR] = 8.0; 95% confidence interval [CI] = 1.0 to 63.7). The relative risk for noncomorbid panic disorder was substantial (RR = 3.6), albeit not statistically significant (95% CI = 0.8 to 17.2). There was no strong evidence for increased risk for phobic disorders or agoraphobia, combined or considered separately, in the 6 months following loss. Relative risk for all 3 disorders combined was 1.5 (95% CI = 0.9 to 2.3). CONCLUSION: In this first miscarriage cohort study using a concurrent frequency-matched comparison group, miscarriage was a substantial risk factor for an initial or recurrent episode of OCD. Given statistical power limitations of this investigation, the current findings do not preclude a possible contribution of miscarriage to risk for other anxiety disorders.

Abortion, Spontaneous↗

Minor depressive disorder in the context of miscarriage.

BACKGROUND: Although minor depressive disorder is of considerable clinical and public health importance, it has received limited research attention relative to major depressive disorder. This study examines the incidence rate and relative risk for minor depressive disorder following miscarriage. METHODS: Using a cohort design we tested whether miscarrying women are at increased risk for an episode of minor depression (diagnosed based on research criteria proposed in Appendix B of DSM-IV) in the 6 months following loss. The miscarriage cohort consisted of women attending a medical center for spontaneous abortion (n=229); the comparison group was a population-based cohort of women drawn from the community (n=230). RESULTS: Among miscarrying women, 5.2% experienced an episode of minor depression, compared with 1.0% of community women. The overall relative risk for an episode of minor depression for miscarrying women was 5.2 (95% confidence interval, 1.2-23.6). Relative risk did not vary by length of gestation at the time of loss or attitude toward the pregnancy. The majority of episodes in miscarrying women began within 1 month following loss. LIMITATIONS: Minor depression was relatively rare in both study cohorts. The resulting limits on statistical power reduced our ability to identify factors, such as sociodemographic or reproductive history variables that might moderate the effect of miscarriage on risk for minor depression. CONCLUSIONS: These results, in the context of prior work showing increased risks of major depression and depressive symptoms following miscarriage, lend some support to the conceptualization of minor depressive disorder as part of a continuum of symptom severity. Miscarrying women should be evaluated for depression at their follow-up medical visits.

Abortion, Spontaneous↗

Prenatal exposure to wartime famine and development of antisocial personality disorder in early adulthood.

CONTEXT: Several observational epidemiological studies report an association of pregnancy and obstetric complications with development of antisocial personality disorder (ASPD) in offspring. However, the precise nature and timing of the hypothesized biological insults are not known. OBJECTIVE: To test whether severe maternal nutritional deficiency early in gestation is associated with risk for ASPD in offspring. DESIGN AND SETTING: Retrospective cohort study. From October 1944 to May 1945, the German army blockaded food supplies to the Netherlands, subjecting the western Netherlands first to moderate (official food rations, 4200-6300 kJ/d) then to severe (<4200 kJ/d) nutritional deficiency. The north and south were subjected to moderate nutritional deficiency only. PARTICIPANTS: Dutch men born in large urban areas in 1944-1946 who were given psychiatric examinations for military induction at age 18 years (N = 100543) were classified by the degree and timing of their prenatal exposure to nutritional deficiency based on their birthdate and birthplace. MAIN OUTCOME MEASURE: Diagnosis of ASPD by psychiatric interview at time of medical examination for military induction, using the International Classification of Diseases, Sixth Revision (ICD-6). RESULTS: Men exposed prenatally to severe maternal nutritional deficiency during the first and/or second trimesters of pregnancy exhibited increased risk for ASPD (adjusted odds ratio [OR], 2.5; 95% confidence interval [CI], 1.5-4.2). Third-trimester exposure to severe nutritional deficiency and prenatal exposure to moderate nutritional deficiency were not associated with risk for ASPD. CONCLUSIONS: Our data suggest that severe nutritional insults to the developing brain in utero may be capable of increasing the risk for antisocial behaviors in offspring. The possible implications of these findings for both developed countries and developing countries, where severe nutritional deficiency is widespread and often exacerbated by war, natural disaster, and forced migration, warrant study.

Adult↗

Witnessed community violence and antisocial behavior in high-risk, urban boys.

Examined the longitudinal relation between children's self-report of witnessing community violence, family environment, and parent report of child antisocial behavior in a sample of 6- to 10-year-old urban American boys (N = 97) at familial risk for antisocial behavior. Boys reported high rates of lifetime exposure to community violence. Boys' reports of witnessing community violence were significantly positively related to changes over 15 months in child antisocial behavior, even after controlling for the possible effects of 3 aspects of parent-child interactions shown previously to be related to problematic child behavior. Furthermore, family environment, particularly the degree to which parents engaged in conflict with their sons, moderated the effect of witnessed violence on changes in antisocial behavior. In families with low conflict, higher levels of witnessed violence predicted increases in antisocial behavior over time. In contrast, in families with relatively high levels of parent-child conflict, high-witnessed violence had no additional influence on antisocial outcome. This is the first prospective longitudinal study to document an association between witnessed community violence and changes in antisocial behavior in young, urban boys at familial risk for antisocial behavior.

Child↗

Darryl, a cartoon-based measure of cardinal posttraumatic stress symptoms in school-age children.

OBJECTIVES: This report examines the reliability and validity of Darryl, a cartoon-based measure of the cardinal symptoms of posttraumatic stress disorder (PTSD). METHODS: We measured exposure to community violence through the reports of children and their parents and then administered Darryl to a sample of 110 children aged 7 to 9 residing in urban neighborhoods with high crime rates. RESULTS: Darryl's reliability is excellent overall and is acceptable for the reexperiencing, avoidance, and arousal subscales, considered separately. Child reports of exposure to community violence were significantly associated with child reports of PTSD symptoms. CONCLUSIONS: Darryl possesses acceptable psychometric properties in a sample of children with frequent exposure to community violence.

Arousal↗

Association of maternal, antenatal and perinatal complications with suicide in adolescence and young adulthood.

The aim of the present study was to investigate whether maternal, antenatal and perinatal complications are associated with adolescent or young adulthood suicide in offspring. Cases consisted of individuals, aged 15-22 years, born in New York City and committing suicide in New York City between 1985 and 1991 (n = 189). Two controls were selected for each case, constituting the hospital birth immediately preceding and following that of the case, matched with the case with regard to sex and ethnicity. Cases were compared with controls using an index that summed a range of maternal, antenatal and perinatal complications and also with regard to the frequency of individual complications. In the total sample, cases and controls did not differ either in the mean number of all complications combined or in the proportions with specific complications. This lack of association between complications and outcome also obtained in separate analyses by sex, ethnicity, socio-economic status and age at suicide. These results fail to replicate the findings of two previous reports implicating maternal, antenatal and perinatal complications in risk of youth suicide. At present, epidemiological evidence that adverse reproductive events increase the risk for suicide in offspring remains inconclusive.

Adolescent↗

Major depressive disorder in the 6 months after miscarriage.

OBJECTIVE: To test a priori hypotheses that miscarrying women are at increased risk for a first or recurrent episode of major depressive disorder in the 6 months following loss and that this increased risk is greater for childless women, women with prior reproductive loss, and women aged 35 years or older; and to evaluate whether risk varies by time of gestation or by attitude toward the pregnancy. DESIGN: Cohort study. SETTING: The miscarriage cohort consisted of women attending a medical center for a spontaneous abortion (n=229); the comparison group was a population-based cohort of women drawn from the community (n=230). PARTICIPANTS: Miscarriage was defined as the involuntary termination of a nonviable intrauterine pregnancy before 28 completed weeks of gestation. Half of all participants were between 25 and 34 years of age; 40% were white and 35% Hispanic; 55% had more than a high school education. Participants constituted 60% of miscarrying women and 72% of community women who completed the first phase of this cohort study. MAIN OUTCOME MEASURE: Major depressive disorder was measured using the Diagnostic Interview Schedule. RESULTS: Risk for an episode of major depressive disorder among miscarrying women in the 6 months following loss was compared with the 6-month risk among community women who had not been pregnant in the preceding year. Among miscarrying women, 10.9% experienced an episode of major depressive disorder, compared with 4.3% of community women. The overall relative risk (RR) for an episode of major depressive disorder for miscarrying women was 2.5 (95% confidence interval [CI], 1.2-5.1) and was substantially higher for childless women (RR, 5.0; 95% CI, 1.7-14.4) than for women with children (RR, 1.3; 95% CI, 0.5-3.5) (P<.06). Among miscarrying women, 72% of cases of major depressive disorder began within the first month after loss; only 20% of community cases started during the comparable period. Among miscarrying women with a history of major depressive disorder, 54% experienced a recurrence. However, RR did not vary significantly by history of prior reproductive loss or by maternal age, nor did risk vary by time of gestation or attitude toward the pregnancy. CONCLUSIONS: Physicians should monitor miscarrying women in the first weeks after reproductive loss, particularly women who are childless or who have a history of major depressive disorder. Where appropriate, supportive counseling or psychopharmacologic treatment should be considered.

Abortion, Spontaneous↗

Association of stressful life events with chromosomally normal spontaneous abortion.

Spontaneous abortion is the most common adverse reproductive outcome. Despite evidence that negative life events increase risk for a number of medical disorders, their role in pregnancy disruption has not been investigated. The present study tested an a priori hypothesis that recent negative life events increase the odds of spontaneous abortion of a chromosomally normal conceptus. Between 1984 and 1986, 192 women aged 18-42 years who visited a medical center after spontaneous abortion were interviewed about positive and negative events that had occurred in the 4-5 months preceding the loss. Subsequently, women with chromosomally normal (n = 111) and chromosomally abnormal (n = 81) losses were identified on the basis of tissue culture after interview. The women with chromosomally abnormal loss provided an estimate of the expected frequency of life events against which to compare the event frequencies of women with chromosomally normal loss. Analyses were adjusted for duration of the recall period, payment status, maternal age, education, and ethnicity. Seventy percent of the women with chromosomally normal losses reported having had one or more negative life events in the months preceding loss, compared with 52% of the women with chromosomally abnormal losses (adjusted odds ratio = 2.6, 95% confidence interval (CI) 1.3-5.2). For private patients (n = 69), the adjusted odds ratio was 4.2 (95% CI 1.3-13.4); for public patients (n = 123), it was 1.9 (95% CI 0.8-4.8). The associations held for postconception events alone and were absent for positive events. Results were unaltered by adjustment for smoking, caffeine intake, and alcohol consumption. With recall bias precluded by the study design, the strength, timing, and specificity of these associations suggest that recent negative life events play a role in chromosomally normal spontaneous abortion. Efforts to replicate these results and to elucidate underlying biologic mechanisms are required.

Abortion, Spontaneous↗