Effect of white mineral trioxide aggregate compared with biomimetic carbonated apatite on dentine bridge formation and inflammatory response in a dental pulp model.

AIM: To evaluate the effects of apatite precipitation on the biocompatibility and hard tissue induction properties of white mineral trioxide aggregate (WMTA) in a dental pulp model. METHODOLOGY: Pulp exposures were created on the axial walls of 32 sound canine teeth of eight dogs. Four additional sound teeth served as controls. The pulps were capped either with WMTA or apatite derivatives [biomimetic carbonated apatite (BCAp)] in the interaction of WMTA with a synthetic tissue fluid and restored with zinc oxide-eugenol cement. After 7 and 70 days, the animals were killed, and the histological specimens taken from the teeth were stained with haematoxylin and eosin for histomorphological evaluation. The Brown and Brenn technique was employed to stain bacteria. The data were subjected to nonparametric Kruskall-Wallis analysis and Mann-Whitney U_tests. RESULTS: Biomimetic carbonated apatite did not induce hard tissue bridge formation. WMTA performed significantly better than BCAp in this respect at both periods (P < 0.05). BCAp was associated with a significantly greater inflammatory response as compared with WMTA after 7 days (P < 0.05). Both materials were associated with similar reactions after 70 days (P >0.05). CONCLUSIONS: White mineral trioxide aggregate induced hard tissue formation via a mechanism other than that postulated via apatite formation.

The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment.

UNLABELLED: Dexmedetomidine, an alpha2-adrenergic agonist with sedative and analgesic properties, is mainly cleared by hepatic metabolism. Because the pharmacokinetics of dexmedetomidine have not been determined in humans with impaired renal function, we studied them in volunteers with severe renal disease and in control volunteers. Six volunteers with severe renal disease and six matched volunteers with normal renal function received dexmedetomidine, 0.6 microg/kg, over 10 min. Venous blood samples for the measurement of plasma dexmedetomidine concentrations were drawn before, during, and up to 12 h after the infusion. Two-compartmental pharmacokinetic models were fit to the drug concentration versus time data. We also determined its hemodynamic, respiratory, and sedative effects. There was no difference between Renal Disease and Control groups in either volume of distribution at steady state (1.81 +/- 0.55 and 1.54 +/- 0.08 L/kg, respectively; mean +/- SD) or elimination clearance (12.5 +/- 4.6 and 8.9 +/- 0.7 mL x min(-1) x kg(-1), respectively). However, elimination half-life was shortened in the Renal Disease group (113.4 +/- 11.3 vs 136.5 +/- 13.0 min; P < 0.05). A mild reduction in blood pressure occurred in most volunteers. Although most volunteers were sedated by dexmedetomidine, renal disease volunteers were sedated for a longer period of time. IMPLICATIONS: The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment differed little from those in volunteers with normal renal function. In addition, there were no clinically significant differences in the hemodynamic responses to dexmedetomidine. However, dexmedetomidine resulted in more prolonged sedation in subjects with renal disease.

Dialysis-related amyloidosis: history and clinical manifestations.

Dialysis-related amyloidosis (DRA) or beta(2)-microglobulin amyloidosis (A beta(2)M) is a unique type of amyloidosis that has been described in individuals with both long-standing chronic renal disease and end-stage renal disease (ESRD). It has been associated with serious complications that significantly add to the morbidity of long-term dialysis patients. The deposition of beta(2)M in amyloid fibrils in various joint and osteoarticular surfaces leads to the clinical complaints and findings typical of this disorder. However, a visceral form with systemic organ involvement has also been described. Despite advances in the understanding of this disorder and in the delivery of dialysis, the ability to alter the incidence of DRA and its course remains uncertain.

Temporal profile of serum-induced S-phase entry and retinoblastoma protein phosphorylation in human skin fibroblasts.

Cultured skin fibroblasts from type 1 diabetic patients with nephropathy have a hyperplastic growth phenotype in comparison with diabetics without nephropathy and controls. We studied the G1 phase cyclins in skin fibroblasts from control subjects to define the temporal profile of serum-induced pRB phosphorylation, cyclin D1 protein expression, and cyclin D1/CDK4(6) kinase activity as well as S-phase entry by FACS analysis. Our preliminary studies indicate that cultured skin fibroblasts from type 1 diabetic patients with nephropathy have an enhanced pRB phosphorylation, cyclin D1 protein expression, and cyclin D1/CDK4(6) kinase activity. This finding may become useful to identify patients at risk for the development of nephropathy.

A subdepressor low dose of ramipril lowers urinary protein excretion without increasing plasma potassium.

Angiotensin-converting enzyme (ACE) inhibitors are increasingly administered to patients with chronic renal disease. One issue of concern with the use of ACE inhibitors in patients with impaired renal function is the possible development of hyperkalemia. We reasoned that the impact of ACE inhibitors on plasma potassium could be minimized by administering these agents at very low doses. To examine this issue, we investigated the effect of a low dose of ramipril (1.25 mg orally once daily) and an eight-fold higher dose (10 mg orally once daily) on plasma potassium in 13 patients with proteinuria and mild chronic renal insufficiency. The study was divided into four phases: placebo (4 weeks), low-dose ramipril (8 weeks), high-dose ramipril (8 weeks), and washout phase (4 weeks). With the low dose of ramipril, urinary protein excretion decreased significantly as early as after 1 week of administration (from 4.4 +/- 0.5 to 3.7 +/- 0.4 g/24 h; P < 0.025) and did not decrease any further thereafter even when the dose was increased eight-fold. Mean arterial blood pressure and plasma potassium did not change significantly with the low dose of ramipril, whereas with the higher dose, mean arterial blood pressure decreased significantly (from 107 +/- 2.0 to 100 +/- 2.0 mm Hg, P < 0.005), and plasma potassium increased significantly (from 4.53 to 4.78 mEq/L, P < 0.05). We conclude that a low dose of ramipril can reduce proteinuria to the same extent as an eight-fold higher dose without significantly lowering blood pressure or increasing plasma potassium. This latter feature may be advantageous for the treatment of patients at risk for hyperkalemia who require ACE inhibitors.

Fatal cervical spondyloarthropathy in a hemodialysis patient with systemic deposition of beta2-microglobulin amyloid.

Destructive spondyloarthropathy is a serious complication in patients with end-stage renal disease. We report a case of fatal cervical spondyloarthropathy in a patient on hemodialysis who presented with severe pain in the cervical area. Magnetic resonance imaging (MRI) of the cervical spine showed a soft tissue mass at the cervico-occipital hinge with spinal cord compression and destructive lesions of the cervical vertebrae. The patient became quadriplegic during the MRI procedure and died a few days later. Postmortem examination showed deposition of beta2-microglobulin in the cervico-occipital hinge. A unique feature of this case was the documented presence of systemic beta2-microglobulin amyloid deposits involving the spleen that to our knowledge has not been reported previously. Clinical suspicion and early detection of lesions caused by dialysis-related amyloidosis (DRA) may help to prevent significant morbidity and mortality in long-term dialysis patients.