Self-referential processing influences functional activation during cognitive control: an fMRI study

Rostral anterior cingulate cortex (rACC) plays a central role in the pathophysiology of major depressive disorder (MDD). As we reported in our previous study (Wagner et al., 2006), patients with MDD were characterized by an inability to deactivate this region during cognitive processing leading to a compensatory prefrontal hyperactivation. This hyperactivation in rACC may be related to a deficient inhibitory control of negative self-referential processes, which in turn may interfere with cognitive control task execution and the underlying fronto-cingulate network activation. To test this assumption, a functional magnetic resonance imaging study was conducted in 34 healthy subjects. Univariate and functional connectivity analyses in statistical parametric mapping software 8 were used. Self-referential stimuli and the Stroop task were presented in an event-related design. As hypothesized, rACC was specifically engaged during negative self-referential processing (SRP) and was significantly related to the degree of depressive symptoms in participants. BOLD signal in rACC showed increased valence-dependent (negative vs neutral SRP) interaction with BOLD signal in prefrontal and dorsal anterior cingulate regions during Stroop task performance. This result provides strong support for the notion that enhanced rACC interacts with brain regions involved in cognitive control processes and substantiates our previous interpretation of increased rACC and prefrontal activation in patients during Stroop task.     

Suggestions for graduate education in nursing service administration

The study was prompted by a long-standing concern about how best to educate nurse administrators for work in complex health service organizations. In the last decade, there has been increasingly widespread agreement in nursing that advanced education for clinical specialization alone may be insufficient. To improve understanding of education for nursing administration (NA), the suggestions in 37 publications printed between 1976 and 1985 were analyzed. Inferences were made from these publications about curriculum content, program structure, instructional placement, and practicum experiences. Content suggested most often pertained to health systems, nursing practice, research, and policy. Reference was least often made to perspectives in organization theory, ethics, and future studies. Suggestions for international NA were made in only one publication. Administration majors with a clinical nursing emphasis in multidisciplinary programs controlled by schools of nursing were widely recommended, as were administrative practicums of variable length. Few suggestions were made about the epistemological considerations needed to guide the development of interdisciplinary nursing administration. In the future, consideration of the overlap--from nursing and management science--of concepts, research problems, and modes of inquiry, will be important for the education of nurse administrators. In the 1960s and early 1970s, clinical specialization was the central focus of graduate nursing education. During this period of time, emphasis on nursing administration (NA) declined, as did the number of NA programs, resulting in a critical shortage of nurse administrators academically prepared to manage health services (Blair, 1976a-b).(ABSTRACT TRUNCATED AT 250 WORDS)     

Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trials.

Although retroviral vectors are one of the most widely used vehicles for gene transfer, there is no uniformly accepted pre-clinical model defined to assess their safety, in particular their risk related to insertional mutagenesis. In the murine pre-clinical study presented here, 40 test and 10 control mice were transplanted with ex vivo manipulated bone marrow cells to assess the long-term effects of the transduction of hematopoietic cells with the retroviral vector MSCV-MGMT(P140K)wc. Test mice had significant gene marking 8-12 months post-transplantation with an average of 0.93 vector copies per cell and 41.5% of peripheral blood cells expressing the transgene MGMT(P140K), thus confirming persistent vector expression. Unexpectedly, six test mice developed malignant lymphoma. No vector was detected in the tumor cells of five animals with malignancies, indicating that the malignancies were not caused by insertional mutagenesis or MGMT(P140K) expression. Mice from a concurrent study with a different transgene also revealed additional cases of vector-negative lymphomas of host origin. We conclude that the background tumor formation in this mouse model complicates safety determination of retroviral vectors and propose an improved study design that we predict will increase the relevance and accuracy of interpretation of pre-clinical mouse studies.     

Memory and the medial temporal lobe: hemispheric specialization reconsidered

The role of the medial temporal lobe in learning and memory has been well established in research on humans and other animals. In humans, clinical and neuroimaging studies typically suggest material-specific lateralization in which the left and right temporal lobes are associated with verbal and nonverbal memory, respectively. It is often assumed that the temporal lobes are functionally alike, differing only in terms of the content to be learned. Here we present data that challenge this notion, showing that the type of material used during a memory task can influence fMRI activation patterns beyond the expected left-verbal/right-nonverbal dichotomy. Our results also suggest some degree of functional asymmetry in the medial temporal lobe that is independent of material type, pointing to underlying processing differences between the left and right temporal lobes.     

Cystatin C, an early indicator for incipient renal disease in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic disease requiring potential nephrotoxic therapy with nonsteroidal antiinflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs). The rationale of our study was to examine the renal status of patients suffering from prolonged RA by means of plasma cystatin C, a new parameter of renal function. Fifty-six patients affected with RA for more than 5 years, and treated with NSAIDs for more than 50 months, were included in the study. Besides conventional markers of renal function (i.e. plasma creatinine, estimated glomerular filtration rate, creatinine clearance), we analysed plasma cystatin C by an automated, nephelometric immunoassay on a Behring nephelometer. Sixty percent of the RA patients exhibited elevated levels of plasma cystatin C, whereas only three out of 56 patients showed an elevated plasma creatinine, even though the creatinine clearance was decreased in 57% of these patients. Cystatin C exhibited a by far better correlation with creatinine clearance than plasma creatinine. In conclusion, patients with prolonged RA for more than 50 months, show a disturbed renal function despite normal plasma creatinine. Elevated cystatin C indicates such incipient renal disease, and is, not least because of a simple, well reproducible technique, more recommendable for screening purposes than tedious clearance determinations.     

The theophylline-enoxacin interaction: I. Effect of enoxacin dose size on theophylline disposition

Theophylline interacts pharmacokinetically with a variety of other drugs. Recently enoxacin was found to change theophylline's disposition. In a four-subject, four-way crossover study enoxacin was administered every 12 hours at four levels (0, 25, 100, and 400 mg) for 14 doses. With the ninth dose of enoxacin, 200 mg theophylline was coadministered. Blood and urine samples were assayed by sensitive and specific assays for the parent drugs and their metabolites. Significant reduction in the formation of theophylline's three major metabolites occurred on coadministration of enoxacin. At the 400 mg dose level, enoxacin caused a threefold decrease in theophylline's plasma clearance, a fourfold decrease in the urinary recovery of 3-methylxanthine and 1,3-dimethylurate, and a threefold decrease in the recovery of 1-methylurate.     

Polymorphisms of the inflammatory system and risk of ischemic cerebrovascular events.

BACKGROUND: Chronic and acute infections are associated with an increased risk of stroke. The inflammatory response can be influenced by functional polymorphisms in components of the immune system. We hypothesized that these polymorphisms may also modulate the risk of ischemic cerebrovascular events. METHODS: We determined the frequency of polymorphisms in tumor necrosis factor-alpha[(TNF-alpha) G(-376)A, G(-244)A, G(-238)A, G(-308)A], Toll-like receptor 4 [(TLR4) Gly299Asp and Thr399Ile], interleukin-1-receptor antagonist [(IL-1-RA) intron 2 variable-number tandem repeat], monocyte differentiation antigen CD14 receptor C(-260)T, and interleukin-6 [(IL-6) G(-174)C] genes in 404 patients with acute stroke or transient ischemic attack before the age of 60 years and in 415 healthy individuals. We also tested for interactions between genotypes, recent febrile episodes and stroke risk. RESULTS: None of the polymorphisms was associated with an increased risk of stroke after adjustment for age and gender. Following multivariate adjustment, carriers of the TNF-alpha (-308)A allele, the IL-1-RA 2* allele or the IL-6 (-174)C allele appeared to have an increased risk of stroke in association with a febrile episode prior to strokes. CONCLUSION: In our study none of the investigated polymorphisms of the inflammatory system was associated with the risk of acute cerebrovascular events before the age of 60 years. However, post-hoc analyses indicate that some polymorphisms seem to contribute to the risk of stroke in combination with fever.     

Chronische Radikulopathie

Zusammenfassung Die Behandlung chronischer Rückenschmerzen mit radikulärer Symptomatik ist ein bis heute nicht gelöstes klinisches Problem. Die von Racz beschriebene Technik der perkutanen minimal-invasiven Neurolyse findet zunehmend Anwendung zur Behandlung der chronischen Radikulopathie. Es wurden 61 Patienten mit einer entsprechenden Symptomatik nach Prüfung der Ein- und Ausschlusskriterien mittels Kathetertechnik nach Racz im Bereich der lumbalen Spinalnerven behandelt. 3 und 6 Monate nach perkutaner minimal-invasiver epiduraler Neurolyse kam es zu einer deutlichen klinischen Verbesserung. Die subjektive Schmerzempfindung, quantifiziert auf dem McNab-Score, zeigte sowohl nach 3 als auch nach 6 Monaten eine deutliche Verbesserung. Mit Ausnahme einer partiellen Katheterabscherung in 2 Fällen und einer Infektion konnten keine relevanten Nebenwirkungen festgestellt werden.Die Kathetertechnik nach Racz ist zur Behandlung der chronischen Radikulopathie nach Bandscheibenoperationen oder Bandscheibenvorfällen geeignet und nebenwirkungsarm.