Comparison of stress-only vs. stress/rest with technetium-99m methoxyisobutylisonitrile myocardial perfusion imaging

Unlike conventional thallium-201 myocardial imaging, technetium-99m methoxyisobutylisonitrile (MIBI) requires separate stress and rest injections. We prospectively studied 148 consecutive patients referred for myocardial perfusion studies to determine the diagnostic value of rest images once normal exercise or dipyridamole tomographic images had been obtained. In patients referred with no history of previous myocardial infarction in whom the diagnosis of coronary artery disease was suspected, 45 of 109 (41%) patients had normal stress tomographic images. Obtaining rest images did not alter the final interpretation in any of these cases. From this we infer that in patients with normal images after exercise or dipyridamole administration and no past history of myocardial infarction, ^99mTc-MIBI rest images are not required. This provides several advantages including increased speed of diagnosis, decreased patient radiation exposure, improved cost efficiency and decreased demand on tomographic camera time. Offprint requests to: A.Y. Fung     

Physiological evaluation of gait disturbances post stroke.

A large proportion of stroke survivors have to deal with problems in mobility. Proper evaluations must be undertaken to understand the sensorimotor impairments underlying locomotor disorders post stroke, so that evidence-based interventions can be developed. The current electrophysiological, biomechanical, and imagery evaluations that provide insight into locomotor dysfunction post stroke, as well as their advantages and limitations, are reviewed in this paper. In particular, electrophysiological evaluations focus on the contrast of electromyographic patterns and integrity of spinal reflex pathways during perturbed and unperturbed locomotion between persons with stroke and healthy individuals. At a behavioral level, biomechanical evaluations that include temporal distance factors, kinematic and kinetic analyses, as well as the mechanical energy and metabolic cost, are useful when combined with electrophysiological measures for the interpretation of gait disturbances that are related to the control of the central nervous system or secondary to biomechanical constraints. Finally, current methods in imaging and transcranial magnetic stimulation can provide further insight into cortical control of locomotion and the integrity of the corticospinal pathways.     

Treatment planning for asymmetric jaws on a commercial TP system.

In this work, the accuracy of the asymmetric jaws planning feature in a commercial treatment planning (TP) system is assessed. In the latest version of this software, the off-axis beam quality variation is handled by a function g(d,r), which is derived from measured horizontal beam profiles at four different depths. The calculated and measured isodoses for a 6-MV linear accelerator with asymmetric jaws agree to +/- 0.5% along the central axis and to within 2 mm at the beam edge. Formulas for treatment time calculations using the output data reported by the computer program are described, as well as formulas for manual calculations based on pregenerated data tables. Doses calculated based on these formulas are compared to measurement and the accuracy is +/- 1% and +/- 2% for the computer and manual calculations, respectively. It is concluded that this version of the treatment planning system as well as the treatment time calculation formulas can be used adequately for asymmetric jaw computerized and manual treatment planning.     

Rectus sheath haematoma requiring laparotomy

Rectus sheath haematoma is a well‐documented but unusual cause of acute abdomen. Combination of clinical features and appropriate radiological investigations can make for a prompt diagnosis. Most authors advocate conservative management and it has been reported that patients were directly discharged from the emergency department. We report a case of rectus sheath haematoma which progressed with clinical deterioration and necessitated surgical intervention for clot evacuation. Causes, physical signs, radiological features and classification of rectus sheath haematoma are discussed. It may be necessary to continue close clinical monitoring after diagnosis of rectus sheath haematoma.     

Immunosuppression in liver transplantation: beyond calcineurin inhibitors.

Although calcineurin inhibitors (CNIs) remain the mainstay of immunosuppression in liver transplantation (LTX), their long-term toxicity significantly contributes to morbidity and mortality. The elucidation of mechanisms of alloimmunity and leukocyte migration have provided novel targets for immunosuppression development. The toxicities of these agents differ from that of the CNI and act additively or synergistically. CNI avoidance protocols in LTX have not been achieved routinely; however, pilot trials have begun to delineate the limitations and promises of such approaches. CNI-sparing protocols appear to be much more promising in balancing the early need for minimizing rejection while tapering doses and minimizing long-term toxicity.     

Influence of hydrophobicity on the ion exchange selectivity coefficients for aromatic amines

Hydrophobic effects could play an important role in determining the selectivity of organic ions for ion-exchange resins in aqueous solutions. We used the octanol-water partition coefficient (P) and the chromatographic capacity factor (K') as indices of hydrophobicity of a series of primary and secondary amines, and examined their relationships with the amine selectivity coefficient (K) in binding to the Amberlite IRP-69 ion-exchange resin. Good correlations were found between log K versus log P and log K versus log K', but the relationship appears to be dependent on the degree of substitution at the amino nitrogen. These relationships may be useful for the estimation of selectivity coefficients of various amine drug candidates when they are considered for incorporation with ion-exchange resins in potential controlled-release systems.     

C-terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties.

We describe the development of a series of soluble, potent, and bioavailable nonpeptide renin inhibitors. These inhibitors derived from a series of novel nonpeptide renin inhibitors which were recently identified in our laboratories, by alteration of the nature of the C-terminus (P2') of the molecules. Introduction of basic substituents into modified hydroxyethylene dipeptide isosteres gave inhibitors with improved solubility as well as improved potency against human plasma renin. In addition, these modifications produced inhibitors which displayed markedly improved intraduodenal bioavailability in both the ferret and cynomolgus monkey. We also present data which demonstrate excellent efficacy in the monkey for A-74273 (65), with an intraduodenal bioavailability of 16 +/- 4% in the monkey, compared to 1.7 +/- 0.5% for the dipeptide renin inhibitor enalkiren (A-64662, 75). A-74273 is an example of a nonpeptide inhibitor which possesses a good balance of the desirable properties of potency, solubility, and lipophilicity and which is well absorbed into the intestine.