Subdental synchondrosis and anatomy of the axis in aging: a histomorphometric study on 30 autopsy cases

During skeletal development the two ossification centers of the odontoid process are separated from the corpus of the axis by a subdental synchondrosis. This synchondrosis is thought to close and disappear spontaneously in adolescence although this has never been studied in detail. The basis of the dens is of clinical relevance as type II dens fractures are located here. To characterize the morphological architecture of the axis with particular attention to the subdental synchondrosis, the complete axis was harvested from thirty age-matched and gender-matched patients of the three different age groups at autopsy. The subdental synchondrosis and the bone structure of the dens, the basis of the dens and the body of C2 were analyzed by radiography, histology and quantitative histomorphometry. At the macroscopic level the persistency of the subdental synchondrosis in the adult cervical spine was detected in 87% (26 of 30) of the specimens. Histomorphometry revealed a residual disc blastema with an average size of 25.8% of the sagittal depth of the basis of the dens at this level. Bony integration of the synchondrosis was poor throughout all ages. Histologically a cartilaginous matrix composition of the subdental synchondrosis persisted throughout all groups. The trabecular microarchitecture demonstrated a significant reduction of bone volume and trabecular number as well as an increased trabecular separation within the basis of the dens as compared to the corpus or the dens of C2. This histomorphometric data regarding a poor integration of the synchondrosis into the trabecular network and the reduced bone mass within the basis of the dens might offer a previously underestimated explanation for the occurrence of type II dens fractures and their association with pseudoarthrosis, respectively.Matthias Gebauer and Christian Lohse contributed equally to this study and therefore share first authorship.     

The REPAIR-AMI and ASTAMI trials: cell isolation procedures: reply

It obviously escaped the notion of Egeland and Brinchman thatthe protocols additionally differ with regard to the washingsteps and buffer components used in the     

Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometry.

Some organophosphorus compounds are toxic because they inhibit acetylcholinesterase (AChE) by phosphylation of the active site serine, forming a stable conjugate: Ser-O-P(O)-(Y)-(XR) (where X can be O, N, or S and Y can be methyl, OR, or SR). The inhibited enzyme can undergo an aging process, during which the X-R moiety is dealkylated by breaking either the P-X or the X-R bond depending on the specific compound, leading to a nonreactivatable enzyme. Aging mechanisms have been studied primarily using AChE. However, some recent studies have indicated that organophosphate-inhibited butyrylcholinesterase (BChE) may age through an alternative pathway. Our work utilized matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry to study the aging mechanism of human BChE inhibited by dichlorvos, echothiophate, diisopropylfluorophosphate (DFP), isomalathion, soman, sarin, cyclohexyl sarin, VX, and VR. Inhibited BChE was aged in the presence of H2O18 to allow incorporation of (18)O, if cleavage was at the P-X bond. Tryptic-peptide organophosphate conjugates were identified through peptide mass mapping. Our results showed no aging of VX- and VR-treated BChE at 25 degrees C, pH 7.0. However, BChE inhibited by dichlorvos, echothiophate, DFP, soman, sarin, and cyclohexyl sarin aged exclusively through O-C bond cleavage, i.e., the classical X-R scission pathway. In contrast, isomalathion aged through both X-R and P-X pathways; the main aged product resulted from P-S bond cleavage and a minor product resulted from O-C and/or S-C bond cleavage.     

α2-adrenoceptor blockade,pituitary-adrenal hormones,and agonistic interactions in rats

The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. α₂ adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an α₂ adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different α₂ adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the α₂ adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.     

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.     

Characterization of a highly polymorphic marker adjacent to the SLC4A1 gene and of kidney immunostaining in a family with distal renal tubular acidosis.

BACKGROUND: Mutations in the human SLC4A1 (AE1/band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain unclear. Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation. METHODS: One CA repeat region was identified in a phage P1-derived artificial chromosome (PAC) clone containing most of the human AE1 gene and the upstream flanking region. We determined its heterozygosity value in multiple populations by PCR analysis. Genotyping of one family with dominant dRTA identified the AE1 R589H mutation, and family member genotypes were compared with the CA repeat length. AE1 and vH(+)-ATPase polypeptides in kidney tissue from an AE1 R589H patient were examined by immunocytochemistry for the first time. RESULTS: This CA repeat, previously reported as D17S1183, is approximately 90 kb upstream of the AE1 gene and displayed considerable length polymorphism, with small racial differences, and a heterozygosity value of 0.56. The allele-specific length of this repeat confirmed co-segregation of the AE1 R589H mutation with the disease phenotype in a family with dominant dRTA. Immunostaining of the kidney cortex from one affected member with superimposed chronic pyelonephritis revealed vH(+)-ATPase-positive intercalated cells in which AE1 was undetectable, and proximal tubular epithelial cells with apparently enhanced apical vH(+)-ATPase staining. CONCLUSIONS: The highly polymorphic dinucleotide repeat adjacent to the human AE1 gene may be useful for future studies of disease association and haplotype analysis. Intercalated cells persist in the end-stage kidney of a patient with familial autosomal dominant dRTA associated with the AE1 R589H mutation. The absence of detectable AE1 polypeptide in those intercalated cells supports the genetic prediction that the AE1 R589H mutation indeed causes dominant dRTA.     

Understanding capture detection.

Automatic capture detection systems are currently available in several cardiac pacing devices. All current systems use low-polarization electrodes and no beat to beat detection system is available for all types of electrodes. In addition the success ratio for currently available systems is not always 100%. Failure to detect capture reliably is often related to the behaviour of the electrode-tissue interface under different circumstances. Pacemaker electrodes can be considered electrochemical cells with complicated characteristics depending on time, temperature and electrical charge. This electrochemical cell is disturbed when a charge is transferred across the electrode-tissue interface during pacing. Several measures can be taken in order to minimise this disturbance or pace polarization artefact (PPA) including the use of high active surface area electrodes and application of tri-phasic pacing pulses. Another factor influencing detection of evoked potentials is the input circuit of the pacemaker affecting the PPA and the evoked response. Positive PPAs can be falsely interpreted as evoked potentials due to the undershoot of the second order filters applied in modern cardiac pacemakers. This paper explains the behaviour of the interface between the electrode and the cardiac tissue in combination with the pacemaker output circuits and input amplifiers under different circumstances.