Effect of manganese chloride and Verapamil on automaticity of digitalized Purkinje fibers.

The effects of manganese chloride (MnCl2) and verapamil on automaticity of digitlazied Purkinje fibers were studied using conventional microelectrode techniques. The stduied wer made in isolated, spontaneously beating Purkinje prearations. Quabain alone consistently increased the automatic rate, whereas no such increase was observed when the preparations were superfused with a mixture of ouabain adn MnCl2. MnCl2 was also shown to be effective is suppressing the enhanced automaticity induced by ouabain. Mncl2 alone did not have a significant effect on the spontaneous rate of Purkinje fibers. The effect of verapamil was similar to that of MnCl2 in preventing and suppressing the ouabain-induced increase in automaticity. MnCl2 and verapamil have been shown to inhibt tha slow inward calcium current of cardiac fibers. The results therefore suggest that an inward calcium ion current may play a role in the development of digitalis-induced increase in the stope of phase 4 depolarization in Purkinje fibers.     

Long-term outcome in patients with chronic atrial fibrillation after successful internal cardioversion

Internal cardioversion is safe and effective in restoring sinus rhythm, even in patients with persistent AF of prolonged duration. Up to 40% to 50% of patients with AF lasting >1 year but <3 years could be maintained in sinus rhythm using a class III antiarrhythmic drug after successful internal cardioversion, and amiodarone appears to be more effective than sotalol in this patient population.     

The Effect of Moving Point of Contact Stimulation on Chondrocyte Gene Expression and Localization in Tissue Engineered Constructs

Tissue engineering is a promising approach for articular cartilage repair. However, using current technologies, the developed engineered constructs generally do not possess an organized superficial layer, which contributes to the tissue’s durability and unique mechanical properties. In this study, we investigated the efficacy of applying a moving point of contract-type stimulation (MPS) to stimulate the production of a superficial-like layer in the engineered constructs. MPS was applied to chondrocyte-agarose hydrogels at a frequency of 0.5, 1 or 2 Hz, under a constant compressive load of 10 mN for durations between 5 and 60 min over 3 consecutive days. Expression and localization of superficial zone constituents was conducted by qRT-PCR and in situ hybridization. Finite element modeling was also constructed to gain insight into the relationship between the applied stimulus and superficial zone constituent expression. Gene expression of superficial zone markers were affected in a frequency dependent manner with a physiologic frequency of 1 Hz producing maximal expression of PRG4, biglycan, decorin and collagen II. In situ hybridization revealed that localization of these markers predominantly occurred at 500–1000 μm below the construct surface which correlated to sub-surface strains between 10 and 25% as determined by finite element modeling. These results indicate that while mechanical stimuli can be used to enhance the expression of superficial zone constituents in engineered cartilage constructs, the resultant subsurface loading is a critical factor for localizing expression. Future studies will investigate altering the applied stimulus to further localize superficial zone constituent expression at the construct surface.     

Treatment with sisomicin of complicated urinary tract infections in patients with varying degrees of renal function impairment

The efficacy, tolerance and pharmacokinetics of the new aminoglycoside antibiotic sisomicin, have been studied in 29 elderly male patients with varying degrees of renal function impairment and suffering from complicated urinary tract infections. The antibiotic was equally effective in patients with normal and impaired renal function and a cure (negative urine culture at one week follow-up) of 56% was obtained. There was little apparent toxicity with the dosage regimens used, although serum creatinine values were statistically but not clinically significantly increased in some patients following treatment. Serum half-lives of sisomicin were prolonged in cases of impaired renal function but accumulation of antibiotic could be prevented by varying dosing intervals between 8 and 24 hours based on serum creatinine values. There was good correlation between serum creatinine and sisomicin serum half-life values and a practical method is described for dose adjustment based on the relationship between serum half-lives and serum creatinine concentrations.