Elimination kinetics of maternally derived thyrotropin receptor-blocking antibodies in a newborn with significant thyrotropin elevation.

OBJECTIVE--To determine the course of maternally derived elevations in thyrotropin-binding inhibitory immunoglobulins in a neonate. DESIGN--Case report. SETTING--University pediatric endocrinology clinic and endocrine immunology laboratory in Ohio. PARTICIPANTS--An infant with elevated thyrotropin levels but near-normal total thyroxine levels, and her mother. INTERVENTIONS--None. MEASUREMENTS/MAIN RESULTS--Thyroid hormone, thyrotropin, and thyrotropin-blocking immunoglobulin concentrations were serially measured in a woman and her infant, who was found to have elevated thyrotropin levels (234 mU/L) and borderline low thyroxine levels (95 nmol/L). As infant thyroxine concentrations remained normal (125 to 145 nmol/L), no thyroxine supplementation was given. Thyrotropin levels decreased concomitantly with thyrotropin-blocking inhibitory immunoglobulin levels, and normalized by day 56 of life. The apparent elimination half-life of thyrotropin-blocking immunoglobulins was 7.5 days. CONCLUSIONS--The observed parallel elimination kinetics suggest that the thyrotropin receptor antibody acts as a thyrotropin antagonist, resulting in compensatory thyrotropin elevations. The duration of such elevations may be predicted on the basis of such elimination.     

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.     

Radiologische und histologische Beobachtungen an zentralen Talusfrakturen

In einer prospektiven Studie zentraler Talusfrakturen wurden radiologische Daten (Nativr?ntgenbild, CT, MRT) auf ihre Korrelation zum histologischen Befund (Biopsie zum Zeitpunkt der Schraubenentfernung) überprüft. Bei 9 Frakturen an 8 Patienten (Alter 14 – 48 Jahre) handelte es sich um Frakturen des Typs Hawkins I und II je einmal sowie des Typs III viermal; in 3 weiteren F?llen lagen K?rperfrakturen vor. Innerhalb von 24 h nach dem Unfall wurden 7 Frakturen verschraubt und 2 mit Bohrdr?hten adaptiert. Das verletzte Bein wurde für 14 – 53 Wochen post trauma vollst?ndig entlastet. Die Beobachtungszeit betrug mit einer Ausnahme 2 Jahre oder mehr; 4 Patienten zeigten am letzten R?ntgenbild einen intakten Talus, 4 Patienten zeigten partielle Einbrüche des Talusdoms und in 1 Fall war ein Teileinbruch fraglich. Die histologische Untersuchung (16 – 52 Wochen post trauma) zeigte in allen F?llen osteozytenfreien origin?ren Knochen mit Anlagerung neuen Knochens in individuell recht unterschiedlichem Ausma?. Das Hawkins-Zeichen war in 6 F?llen partiell positiv, sowie je einmal positiv und einmal negativ. Im CT konnte sowohl Dekalzifikation als auch Frakturheilung besser als im R?ntgenbild beobachtet werden. Das MRT-Signal war 5mal normal, 2mal partiell und einmal komplett pathologisch. Positives Hawkins-Zeichen und normales Signalverhalten sind prognostisch günstig zu werten. Es kam jedoch in Folge zentraler Talusfraktur auch bei radiologisch günstigem Verlauf zur Osteonekrose wenigstens von Teilen Talus gefolgt von schleichendem Ersatz. Die offenbar bei jeder zentralen Talusfraktur gest?rte Vaskularisation wurde von keinem radiologischen Befund einwandfrei reflektiert.      

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.     

Dyslipidemia and nephrotic syndrome: recent advances.

Patients with nephrotic syndrome (NS) have one of the most pronounced secondary changes in lipoprotein metabolism known, and the magnitude of the changes correlates with the severity of the disease. These changes are of a quantitative as well as a qualitative nature. All apolipoprotein B (apo B)-containing lipoproteins, such as very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and lipoprotein(a) [Lp(a)], are elevated in nephrotic syndrome. High-density lipoproteins (HDL) are reported to be unchanged or reduced. In addition to these quantitative changes, the lipoprotein composition is markedly changed, with a higher ratio of cholesterol to triglycerides in the apo B-containing lipoproteins and an increase in the proportion of cholesterol, cholesterol ester, and phospholipids compared with proteins. Also apolipoproteins show major changes, with an increase in apolipoprotein A-I, A-IV, B, C, and E. Particularly the changes in apo C-II, which is an activator of the enzyme lipoprotein lipase (LPL), and apo C-III, an inhibitor of LPL, with an increase of the C-III to C-II ratio, might contribute to the impaired lipoprotein catabolism in NS. The mechanisms for these changes in lipoprotein metabolism are discussed in this review as far as they are known. Furthermore, the tremendous elevations of Lp(a) in nephrotic syndrome and its primary and secondary causes are reviewed. Primary causes became recently apparent by a significantly higher frequency of low-molecular-weight apo(a) phenotypes in patients compared with controls. The secondary causes were shown by an increase of Lp(a) in all apo(a) isoform groups. Because Lp(a) is an LDL-like particle that is usually included in the measured or calculated LDL cholesterol fraction, the influence of the extremely high Lp(a) levels in NS on the measurement of LDL cholesterol is discussed.     

Differential effect of catechol-O-methyltransferase Val158Met genotype on emotional recognition abilities in healthy men and women.

The catechol-O-methyltransferase (COMT) Val158Met polymorphism modulates executive functions and working memory and recent neuroimaging studies implicate an association with emotional processing. We examined the relationship between the COMT Val158Met polymorphism and facial emotion recognition and differentiation in 100 healthy individuals. Compared to Met homozygosity, Val homozygosity was associated with better and faster recognition of negative facial expressions such as anger and sad. Our study provides evidence for a possible influence of the COMT polymorphism on emotion recognition abilities in healthy subjects. Additional research is needed to further define the neurocognitive phenotypes associated with COMT polymorphisms.