The aim of the present study was to determine the tactile pressure thresholds perceived with dental implants during a three-month healing phase following implant placement (osseointegration phase). The absolute threshold of tactile perception was measured in a group of patients 1 week, 1, 2 and 3 months following implant placement (ITI Dental Implant System, Straumann AG, Waldenburg, Switzerland). Contralateral and neighbouring teeth were measured at the same time. For determination of the axial forces exerted on the implants and teeth, and electronic device with semi-conductor strain gauges was used (Hämmerle et al. 1995). The results demonstrated mean thresholds of tactile perception for the implants of 160.2 g (SD 61.7 g, range 77 approximately 283 g) at 1 week, 133.4 g (SD 51.9 g, range 32 approximately 239 g) at 1 month, 147.9 g (SD 53.5 g, range 70 approximately 257 g) at 2 months, and 146.9 g (SD 57.4 g, range 77 approximately 248 g) at 3 months. Statistical analysis using Student's paired t-test revealed no significant differences between the values over time. The control teeth exhibited mean values for tactile perception of 13.1 g (SD 9.6 g, range 5 approximately 47 g) at 1 week, 10.2 g (SD 6.4 g, range 4 approximately 29 g) at 1 month, 14.8 g (SD 15.9 g, range 2 approximately 58 g) at 2 months, and 15.4 g (SD 12.2 g, range 3 approximately 36 g) at 3 months. Again, these values did not differ significantly from each other and indicated the absence of systemic alterations in perceived pressure threshold over the observation period. The mean perceived pressure threshold was more than 10 times higher for implants than for natural teeth (P < 0.001) at all observation times. It is concluded that the absolute threshold of tactile perception with dental implants during the phase of osseointegration is not affected by bone and soft tissue healing taking place during the time period.

ImportanceIn patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited.ObjectiveTo report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial.Design, Setting, and ParticipantsSURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021.InterventionPatients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis.Main Outcomes and MeasuresThe prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years.ResultsA total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention.Conclusions and RelevanceAmong intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Bioactive primary and secondary amines, when acylated with the Z-Gly-Phe group, are transported into pinocytic cells, such as macrophages, P-815 mastocytoma, SV-40 3T3, and leukemia 1210, much faster than the parent compounds. Amines such as lysosomotropic detergents [R. A. Firestone, J. M. Pisano, and R. J. Bonney, J. Med. Chem., 22, 1130 (1979) and nitrogen mustard, which are deactivated by acylation, are unmasked by enzymic action intracellularly, probably in lysosomes because an acidic pH maximum in activity exists which acts only on the L isomer. The added polarity and molecular weight brought about by acylation prevents the amines' normally facile entry into cells by simple diffusion, restricting it to an active-transport mechanism.

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