Functional and reactive hyperemia are unaltered by homocysteine in conscious dogs

Summary The purpose of this study was to test the hypothesis that L-homocysteine thiolactone (L-HCTL), through its reaction with adenosine to formS-adenosylhomocysteine, may modulate myocardial functional and reactive hyperemic responses. Reactive hyperemic responses to 10-sec occlusions or 400-msec diastolic occlusions of the circumflex coronary artery and functional hyperemic responses to ventricular extra-activations were studied in a chronic heart-blocked dog preparation during a control period and following L-HCTL (40 mg/kg). In two additional dogs multiple venous blood samples and left ventricular myocardial biopsies were obtained following L-HCTL to measure changes in plasma homocysteine and tissueS-adenosylhomocysteine. Despite a 75-fold increase in peak plasma homocysteine and a 26-fold increase in tissueS-adenosylhomocysteine, L-HCTL did not alter myocardial functional and reactive hyperemic responses.The rapid increase in myocardialS-adenosylhomocysteine confirmed cellular entry of homocysteine and its reaction with endogenous adenosine. The failure of L-HCTL to alter functional and reactive hyperemic responses suggests that either such treatment does not affect myocardial release of adenosine or that adenosine is not an important regulator of coronary flow.Supported in part by the National Institutes of Health Grants HL 18468 and AM 12828 and the Medical Research Service of the Veterans Administration. Dr. Sadick is a recipient of an Overseas Research Fellowship from the Australian National Heart Foundation. Parts of this work were presented at the 56th Scientific Sessions, American Heart Association, Anaheim, California, November, 1983.     

Designing a complete-arch digital trial tooth arrangement for completely edentulous patients by using an open-source CAD software program: A dental technique

A method for creating a complete-arch digital trial tooth arrangement for completely edentulous patients is described. The technique demonstrates an effective way to reproduce the dental and gingival anatomies by using a free 3D modeling software program. This cost-effective, time-saving, and versatile method allows dental professionals to digitally plan challenging treatments for completely edentulous patients. The technique can also be used to fabricate diagnostic prostheses and implant-supported interim prostheses.     

Observational Study Mortality in Treated Primary Aldosteronism: The German Conn's Registry

In comparison with essential hypertension, primary aldosteronism (PA) is associated with an increased risk of cardiovascular morbidity. To date, no data on mortality have been published. We assessed mortality of patients treated for PA within the German Conn's registry and identified risk factors for adverse outcome in a case-control study. Patients with confirmed PA treated in 3 university centers in Germany since 1994 were included in the analysis. All of the patients were contacted in 2009 and 2010 to verify life status. Subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg served as controls. Final analyses were based on 600 normotensive controls, 600 hypertensive controls, and 300 patients with PA. Kaplan-Meyer survival curves were calculated for both cohorts. Ten-year overall survival was 95% in normotensive controls, 90% in hypertensive controls, and 90% in patients with PA (P value not significant). In multivariate analysis, age (hazard ratio, 1.09 per year [95% CI, 1.03-1.14]), angina pectoris (hazard ratio, 3.6 [95% CI, 1.04-12.04]), and diabetes mellitus (hazard ratio, 2.55 [95% CI, 1.07-6.09]) were associated with an increase in all-cause mortality, whereas hypokalemia (hazard ratio, 0.41 per mmol/L [95% CI, 0.17-0.99]) was associated with reduced mortality. Cardiovascular mortality was the main cause of death in PA (50% versus 34% in hypertensive controls; P<0.05). These data indicate that cardiovascular mortality is increased in patients treated for PA, whereas all-cause mortality is not different from matched hypertensive controls.     

Using bearing area parameters to quantify early erosive tooth surface changes in enamel: A pilot study

Objectives

Most in vitro studies investigate the erosive process using relatively simple roughness parameters such as roughness average (R_a). In isolation, R_a may misrepresent the surface features. Further, few studies report baseline surface characteristics after sample preparation. This study aimed to test the hypothesis that measuring the bearing area parameters in addition to R_a may be useful when qualifying the surface of enamel at baseline and after an erosive challenge. The null hypothesis for this study was that the bearing area parameters provide no more useful information than R_a alone, when qualifying the surface of enamel at baseline and after an erosive challenge.

Methods

Enamel slabs (n = 20) were prepared from human (n = 2) and bovine (n = 4) incisor teeth and polished with 0.05 μm paste. Roughness average (R_a) and bearing parameters (MR1, MR2, R_pk, R_k, R_vk) were used to record baseline characteristics. Specimens were subjected to erosion with 1% citric acid solution for 1 min. Profilometric characteristics were recorded post-erosion, along with the maximum height changes within the profile. T-tests were carried out in order to compare baseline surface characteristics between tissue types. Post-erosion, analysis of variance (ANOVA) was used to test the effects of tissue type (bovine or human).

Results

There was no significant difference in R_a between human and bovine incisor enamel at baseline (human 0.11 μm, bovine 0.12 μm P > 0.05), and no significant difference was observed post-erosion (human 0.23 μm, bovine 0.20 μm P > 0.05). There were significant differences in bearing parameters at baseline and post-erosion that were not identified by the R_a measurement alone.

Conclusions

The results suggest that if R_a alone is measured, important differences in surface characteristics may be missed. The null hypothesis is rejected, and the recommendation is made that bearing parameters are included within profile measurements in order to further triangulate the results of surface analysis studies.

Clinical relevance

In isolation, R_a may misrepresent the surface features of a profile. These results have shown that the bearing parameters are an important and informative set of measurements. The recommendation is made that bearing parameters are included within profile measurements at baseline and post-erosion, in order to further triangulate the results of surface analysis studies.     

Treatment with Thalidomide and Cyclophosphamide (TCID) is Superior to Vincristine (VID) and to Vinorelbine (VRID) Regimens in Patients with Refractory or Recurrent Multiple Myeloma

Treatment of relapsed or refractory multiple myeloma remains a challenge and novel treatment regimen are required. Here, a matched pair analysis was performed comparing TCID (thalidomide, cyclophosphamide, idarubicin, dexamethasone) treatment to the treatment of patients with VID (vincristine, idarubicin, dexamethasone) or with VRID (vinorelbine, idarubicin, dexamethasone) for relapsed or refractory multiple myeloma. In total, 197 patients were enrolled in multicenter trials. After matching for important prognostic variables 46 matched-pairs (total of 138 patients) could be analysed with regard to survival, toxicity and efficacy. Interestingly, a significant improvement of overall response rate (ORR) for TCID treatment compared to VID and VRID was found. In addition, TCID treatment also led to a significantly higher overall survival (OS) as well as progression-free survival (PFS) compared to VID and VRID. In conclusion, TCID treatment appears to be superior to VRID and VID treatment in patients with progressive or refractory myeloma.