Immunoglobulin Gene Rearrangement in Plasma Cell Dyscrasias: Detection of Small Clonal Cell Populations in Peripheral Blood and Bone Marrow

The bone marrow (BM) and peripheral blood (PB) samples of 71 patients with plasma cell dyscrasias were analysed by the Southern blot technique for the presence of clonal immunoglobulin (Ig) gene rearrangements. 53% of BM samples examined were archival material such as air dried BM slides or frozen trephine biopsies. The results were related to bone marrow plasmacytosis as determined by cytology and flow cytometry, and other clinical parameters. Clonal Ig gene rearrangements were found in BM samples of 45 (83%) of 54 MM patients and in 3 of 6 patients with monoclonal gammopathy of unknown significance (MGUS). Clonal cell populations in the PB were detected in 11 (30%) of 37 examined MM patients, but in none of the patients with MGUS or solitary plasmacytoma of bone. PB involvement was associated with progressive disease. Circulating monoclonal cells were significantly associated with higher M-protein levels (p 0.05). Thus, circulating clonal precursor cells are encountered more frequently in active MM.     

Influence of Electromagnetic Fields on Function of Automated External Defibrillators

Objectives: In this study, the authors tested whether electromagnetic interference (EMI) is able to impair correct electrocardiogram analysis and produce false‐positive shock advice from automated external defibrillators (AEDs) when the true rhythm is sinus. Methods: Nineteen healthy subjects were used to test five AEDs available on the Austrian market in a prospective, open, and sequence‐randomized study. The primary outcome variable was the absolute number of shocks advised in the presence of EMI. The secondary outcome was the number of impaired analyses caused by incorrectly detected patient movements or electrode failure. Results: Of 760 tests run, 18 (2.37%) cases of false‐positive results occurred, and two of five AEDs recommended shocks in the presence of sinus rhythm. Of 760 tests run, no electrode failures occurred. There were 27 occurrences (3.55%) of motion detected by an AED in the presence of strong electromagnetic fields. Conclusions: AED models differ in their response to EMI; it may be useful to consider specific safety requirements for areas with such fields present. Working personnel and emergency medical services staff should be informed about potential risks and the possible need for patient evacuation before AEDs are attached and shock recommendations are followed.     

Electrodynamics and ultimate SNR in parallel MR imaging.

The purpose of this article is to elucidate inherent limitations to the performance of parallel MRI. The study focuses on the ultimate signal-to-noise ratio (SNR), which refers to the maximum SNR permitted by the electrodynamics of the signal detection process. Using a spherical model object, it is shown that the behavior of the ultimate SNR imposes distinct limits on the acceleration rate in parallel imaging. For low and moderate acceleration, the ultimate SNR performance is nearly optimal, with geometry factors close to 1. However, for high reduction factors beyond a critical value, the ultimate performance deteriorates rapidly, corresponding to exponential growth of the geometry factor. The transition from optimal to deteriorating performance depends on the electrodynamic characteristics of the detected RF fields. In the near-field regime, i.e., for low B0 and small object size, the critical reduction factor is constant and approximately equal to four for 1D acceleration in the sphere. In the far-field wave regime the critical reduction factor is larger and increases both with B0 and object size. Therefore, it is concluded that parallel techniques hold particular promise for human MR imaging at very high field.     

Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity.

Corticotropin-releasing hormone receptor type 1 (CRH-R1)-deficient mice display reduced anxiety-like behavior, a chronic corticosterone deficit, and an impaired neuroendocrine stress response caused by disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. The molecular substrates and pathways of CRH/CRH-R1-dependent signaling mechanisms underlying the behavioral phenotype as well as the consequences of lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling of brains of CRH-R1 mutant and wild-type mice using our custom made MPIP (Max Planck Institute of Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered expression levels when comparing CRH-R1 knockout mice with wild-type littermates. A significant proportion of differentially expressed genes was related to control of HPA and hypothalamic-pituitary-thyroid (HPT) axes reflecting not only the disturbance of the HPA axis in CRH-R1 mutant mice but also the interplay of both neuroendocrine systems. The spatial analysis of regulated genes revealed a prevalence for genes expressed in the cerebral microvasculature. This phenotype was confirmed by the successful cross-validation of regulated genes in CRH overexpressing mice. Analysis of the cerebral vasculature of CRH-R1 mutant and CRH overexpressing mice revealed alterations of functional rather than structural properties. A direct role of the CRH/CRH-R1 system was supported by demonstrating Crhr1 expression in the adult murine cerebral vasculature. In conclusion, these data suggest a novel, previously unknown role of the CRH/CRH-R1 system in modulating neurovascular gene expression and function.     

Laparoscopic Versus Open Renal Procurement for Pediatric Recipients of Living Donor Renal Transplantation

Despite reports demonstrating the safety of laparoscopic donor nephrectomy (LDN) for pediatric recipients of renal transplants, recent evidence has challenged using LDN for recipients 5 years of age or younger. We retrospectively reviewed the records of all pediatric recipients of living donor renal transplants from September 2000 through August 2004. We compared those who received allografts recovered by LDN (n = 34) with those recovered by open donor nephrectomy (ODN, n = 26). Outcomes of interest included operative complications, postoperative renal function, the incidence of delayed graft function or episodes of acute rejection and long-term graft function. Donor and recipient demographic data were similar for the LDN and ODN groups. Serum creatinine and calculated creatinine clearance were not significantly different between groups both in the early postoperative period and at long-term follow-up (p > 0.142). Rates of delayed graft function and acute rejection did not differ between groups. Among recipients aged 5 years old or younger stratified by donor technique (9 LDN, 5 ODN recipients), no difference was noted in graft outcomes both early and long-term (p > 0.079). At our center, pediatric LDN recipients have graft outcomes comparable to those of ODN recipients. At experienced centers, we recommend continued use of LDN for pediatric recipients of all ages.     

An imaging routine for assessing the efficacy of instruments used for scaling and root planning

Deposits of dental plaque or calculus are typically quantified using planimetric techniques. However, error is introduced into a quantitative analysis of plaque deposits using these methods, since they require a significant amount of human intervention. The purpose of this study is to describe and validate a computerized imaging routine which has the potential to objectively identify material on dental roots and measure the area covered by these deposits. Dentiform teeth with simulated plaque were videorecorded. A computer routine was developed based on a flood-fill algorithm which analyzed images of the dentiform teeth and determined the amount of simulated plaque on their root surfaces. Results showed that the dentiform teeth and their simulated plaque patterns are duplicated by the imaging routine in a rapid and reliable fashion. The system shows a high degree of accuracy with an average error factor of only 0.58%. As well, the system enables precise reproducibility with an average error factor of only 0.71%.     

Growth factor responsiveness of human retinal pigment epithelial cells

Growth factor effects on DNA synthesis in density-arrested human retinal pigment epithelial cells were assessed by [3H]-thymidine incorporation. Acidic and basic fibroblast growth factor and epidermal growth factor were potent stimulators, whereas platelet-derived growth factor, insulinlike growth factor-1, and insulin were weak or modest stimulators when used alone. When used in combination, each of the above growth factors caused a significant enhancement of [3H]-thymidine incorporation regardless of its effect when used alone. The combination of all four growth factors was significantly more effective than all other combinations, demonstrating synergism in their action. Similar results were found in cell proliferation assays. In contrast to this, transforming growth factor-beta inhibited the ability of each of the other growth factors and serum-containing media to stimulate [3H]-thymidine incorporation. These data suggest that DNA synthesis in human retinal pigment epithelial cells can be modulated by several growth factors, some in a stimulatory or synergistic manner and at least one in an inhibitory manner. A better understanding of these complex interactions may provide insights relevant to normal and abnormal ocular wound healing.     

T cell subsets mediating rejection of established fetal pancreas grafts and failure to observe graft adaptation

The present study has attempted to elucidate the cellular mechanisms by which long-term established fetal pancreas allografts are rejected. We used an experimental model in which H-2b nude mice were made hyperglycemic by streptozotocin treatment and then engrafted with allogeneic fetal pancreas grafts. These grafts were functional in that engrafted animals returned to near normoglycemia while all animals left unengrafted subsequently died. The fetal pancreas grafts were allowed to reside in the immunoincompetent nude host for 6-9 months prior to T cell reconstitution, at which time animals were reconstituted with either negatively selected CD4+ or CD8+ H-2b T cell subpopulations. We found that a 6-9 month residence in an immunoincompetent host did not lead to a change in the immunogenicity of fetal pancreatic grafts in that both CD4+ and CD8+ T cell subsets were capable of rejecting these long-term established fetal pancreas grafts. The finding that isolated CD8+ spleen T cell subpopulations, which are only activated by antigen-presenting cells of donor origin bearing MHC class I alloantigen, were capable of effecting graft rejection suggested that APC of donor origin persisted in these long-term fetal pancreas allografts.     

Altered corticomotor representation in patients with Parkinson's disease.

In 6 patients with Parkinson's disease (PD) and 6 age-matched controls, transcranial magnetic stimulation was applied at 56 regions over the motor cortex and premotor cortex of each hemisphere, with the first dorsal interosseous (FDI) muscle of both hands activated at 15% maximum voluntary contraction during stimulation. For each site, motor evoked potential (MEP) landmarks were recovered, including MEP amplitude, MEP onset latency, and silent period duration. Scaled MEP amplitudes were used to construct individual cortical maps of the FDI muscles. The maps revealed an anterior displacement of the muscle representation in PD patients. This anterior shift over motor cortical areas may reflect increased contributions of corticocortical connections between motor cortex and premotor cortical areas, possibly enhanced by the visual feedback aspect of the task. These alterations may reflect adaptations to the impairments in striatocortical circuits in PD.