Bisphosphonate (pamidronate/APD) prevents arthritis-induced loss of fracture toughness in the rabbit femoral diaphysis

Patients with rheumatoid and other inflammatory arthritis have an increased risk for fracture. This study was designed to determine the effect of experimental inflammatory arthritis on the material properties (fracture toughness and shear modulus) and structural properties (torque, angular defelection, and absorbed energy) of femoral diaphyseal bone tested in torsion to fracture, as well as the effect on these properties of APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate), a drug known to block osteoclast activity. Two dose levels were investigated. Experimental inflammatory arthritis was induced by intra-articular injection of carrageenan into the right tibiofemoral joint, given over 7 weeks, in three groups of animals. Simulataneously, daily subcutaneous injections of APD were given to three groups of rabbits. Five groups (12 animals each) were established: normal, arthritis, normal/high dose APD, arthritis/high dose APD, and arthritis/low dose APD. The diaphyses of each excised right femur were loaded to fracture in torsion at an angular deflection rate of 8°/sec. In the arthritis group, the fracture toughness was 39% lower than in the normal group, and the structural properties all were reduced significantly. By contrast, the shear modulus was unaffected by arthritis. In this study, the higher dose level (0.3 mg/kg of body weight) of APD prevented loss of fracture toughness and maintained the structural properties in experimental inflammatory arthritis; the low dose was not effective.     

Volatile General Anesthetics Produce Hyperpolarization of Aplysia Neurons by Activation of a Discrete Population of Baseline Potassium Channels

Background: The mechanism by which volatile anesthetics act on neuronal tissue to produce reversible depression is unknown. Previous studies have identified a potassium current in invertebrate neurons that is activated by volatile anesthetics. The molecular components generating this current are characterized here in greater detail.

Methods: The cellular and biophysical effects of halothane and isoflurane on neurons of Aplysia californica were studied. Isolated abdominal ganglia were perfused with anesthetic-containing solutions while membrane voltage changes were recorded. These effects were also studied at the single-channel level by patch clamping cultured neurons from the abdominal and pleural ganglia.

Results: Clinically relevant concentrations of halothane and isoflurane produced a slow hyperpolarization in abdominal ganglion neurons that was sufficient to block spontaneous spike firings. Single-channel studies revealed specific activation by volatile anesthetics of a previously described potassium channel. In pleural sensory neurons, halothane and isoflurane increased the open probability of the outwardly rectifying serotonin-sensitive channel (S channel). Halothane also inhibited a smaller noninactivating channel with a linear slope conductance of approximately 40 pS. S channels were activated by halothane with a median effective concentration of approximately 500 micro Meter (0.013 atm), which increased channel activity about four times. The mechanism of channel activation involved shortening the closed-time durations between bursts and apparent recruitment of previously silent channels.     

Fetal Oxygen Saturation Monitoring in Labour: An Analysis of 118 Cases

Summary: Fetal oxygen saturation (FSpO₂) was recorded during labour to determine the relationship between FSpO₂ and indicators of fetal well-being, including umbilical blood gases, xanthine (X), hypoxanthine (Hx) and Apgar scores. This is one of me largest reported series of fetal pulse oximetry, with 118 fetuses monitored for over 329 hours. Mean FSpO, for all cases was 46.9% (SD=9.1%). There was no correlation between FSpO, during the last 10 minutes of monitoring and arterial pH, Hx or X. A mean FSpO₂, ≤ 30% was associated with a 5 minute Apgar score of ≤ 7 in the majority of cases. One fetus had a mean FSpO₂, <30% during the final 10 minutes of monitoring and an umbilical arterial pH<7.20, while there were 10 fetuses with an umbilical arterial pH<7.20, and mean FSpO₂, ≥ 30%. As these numbers are small, a larger series is necessary to further characterize the small number of fetuses who are significantly hypoxic.     

Radionuclide bone/joint imaging in children with rheumatic complaints

We reviewed the medical records and technetium bone/joint scans of 160 children presenting to the inpatient Pediatric Rheumatology service over a 3-year period. When the scan result (normal versus abnormal) was considered for each patient as a whole, scan sensitivity and specificity were both approximately 75%. However, when each joint was considered individually, sensitivity decreased to 37%, while specificity rose to more than 95% when compared to clinical examination. Reasons for these variations and their clinical correlation are discussed. Overall, radionuclide bone/joint scanning was found to be very useful in the evaluation of monoarticular and nonrheumatic disorders, but it did not alter therapy in children with known connective tissue disorders or other polyarticular diseases.     

A new epitope on human myelin basic protein arising from cleavage by a metalloendoprotease associated with brain myelin membranes

Human brain myelin membranes were incubated to allow activity of an associated metalloendoprotease which cleaves myelin basic protein (MBP). A 10.3 kDa C-terminal fragment of MBP, peptide C, isolated from the incubation medium had a blocked N-terminal. After treatment with pyroglutamyl aminopeptidase, N-terminal sequencing indicated that Gln74 of MBP formed the N-terminal residue of peptide C. A rabbit antiserum was raised to a synthetic peptide containing the sequence Pyroglu-Lys-Ser-His-Gly-Arg, corresponding to the first six residues of peptide C. By immunoblotting this serum reacted with peptide C but not with intact MBP. The data indicate that cleavage of MBP by a myelin-associated protease engenders a new epitope.     

ENERGY COST OF WALKING AND OF WHEELCHAIR PROPULSION BY CHILDREN WITH MYELODYSPLASIA: COMPARISON WITH NORMAL CHILDREN

The oxygen consumption of 15 myelodysplastic children during walking and propelling a wheelchair was studied. In comparison to normal children, they walked more slower and consumed more oxygen per meter, but had a similar rate of oxygen consumption. A swing-through gait pattern was 33 per cent more energy-efficient than a four-point gait pattern for these children. Wheelchair propulsion produced velocities and energy efficiencies similar to normal children walking. Oxygen consumption and velocity measurements were found to be significantly related to the clinical factors of level of lesion and strength of hip and knee extension. Regression lines and equations are presented to permit prediction of energy cost and efficiency from heart-rate data of myelodysplastic children.     

Primary malignant mesenchymoma of bone: case report,literature review,and distinction of this entity from mesenchymal and dedifferentiated chondrosarcoma

The seventh case of primary malignant mesenchymoma of bone is reported. It is compared to the other six cases in the literature and a clinicopathologic pattern of this entity is developed. Primary malignant mesenchymoma of bone is compared to mesenchymal chondrosarcoma and dedifferentiated chondrosarcoma. Differences as well as similarities are discussed and a more current classification scheme for malignant mesenchymoma of bone is proposed.