Multidetector computed tomography coronarography: preliminary experience in real life settings

Multidetector computed tomography coronarography (MDCT) is a promising tool, offering non invasive anatomic evaluation of coronary arteries. We relate in this article our impressions after our first two years experience. METHODS: Retrospective study of the 328 patients who underwent MDCT examination between January 2005 and December 2006 at our community hospital. Per patient comparative analysis of the anatomical findings versus percutaneous angiography (PCA) in 61 cases. RESULTS: Out of 328 patients 61 (18.5%) underwent PCA. In these patients we found a sensibility, specificity, positive predictive value and negative predictive value of 100%, 54%, 59% and 100% for MDCT. The main factor responsible for inconclusive vessel analysis was excessive calcification. CONCLUSION: In routine use, MDCT enables one to rule out significant stenosis non invasively, with high sensitivity in an unselected patient population.     

Pyridoxamine reduces methylglyoxal and markers of glycation and endothelial dysfunction,but does not improve insulin sensitivity or vascular function in abdominally obese individuals: A randomized double-blind placebo-controlled trial

Aim

To investigate the effects of pyridoxamine (PM), a B6 vitamer and dicarbonyl scavenger, on glycation and a large panel of metabolic and vascular measurements in a randomized double-blind placebo-controlled trial in abdominally obese individuals.

Materials and methods

Individuals (54% female; mean age 50 years; mean body mass index 32 kg/m²) were randomized to an 8-week intervention with either placebo (n = 36), 25 mg PM (n = 36) or 200 mg PM (n = 36). We assessed insulin sensitivity, β-cell function, insulin-mediated microvascular recruitment, skin microvascular function, flow-mediated dilation, and plasma inflammation and endothelial function markers. PM metabolites, dicarbonyls and advanced glycation endproducts (AGEs) were measured using ultra-performance liquid chromatography tandem mass spectrometry. Treatment effects were evaluated by one-way ANCOVA.

Results

In the high PM dose group, we found a reduction of plasma methylglyoxal (MGO) and protein-bound Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), as compared to placebo. We found a reduction of the endothelial dysfunction marker soluble vascular cell adhesion molecule-1 (sVCAM-1) in the low and high PM dose group and of soluble intercellular adhesion molecule-1 (sICAM-1) in the high PM dose, as compared to placebo. We found no treatment effects on insulin sensitivity, vascular function or other functional outcome measurements.

Conclusions

This study shows that PM is metabolically active and reduces MGO, AGEs, sVCAM-1 and sICAM-1, but does not affect insulin sensitivity and vascular function in abdominally obese individuals. The reduction in adhesion markers is promising because these are important in the pathogenesis of endothelial damage and atherosclerosis.     

Early onset of action and efficacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis

BACKGROUND: Calcipotriene and betamethasone dipropionate are topical treatments for psoriasis vulgaris. Their mode of action is different. Improved risk/benefit may result with concomitant use of the two compounds together. A new vehicle has been created with the objective of obtaining optimal stability of both calcipotriene and betamethasone dipropionate in the combination product. OBJECTIVE: We compared the clinical efficacy of a fixed combination of calcipotriene and betamethasone dipropionate in a new vehicle to calcipotriene in the new vehicle, betamethasone in the new vehicle, and the new vehicle alone. METHODS: This was an international, multicenter, prospective, randomized, double-blind, parallel-group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. RESULTS: The mean percentage reduction in PASI from baseline to end of treatment was 73.2% in the combination group (n = 301), 48.8% in the calcipotriene group (n = 308), 63.1% in the betamethasone dipropionate group (n = 312) and 28.8% in the new vehicle group (n = 107), (P < .001). The mean percentage reduction in PASI during the first week was 48.1%, 28.4%, 41.4%, and 21.5%, respectively (P < .001). CONCLUSION: A combination product of calcipotriene 50 microg/g and betamethasone dipropionate 0.5 mg/g in the new vehicle shows superior efficacy with a more rapid onset of action than the new vehicle containing either constituent alone in the treatment of psoriasis vulgaris.     

Determination of the solute removal index for urea by using a partial spent dialysate collection method

In 22 hemodialysis patients, during a dialysis session, the solute removal index (SRI) for urea obtained from the use of a partial spent dialysate collection method was compared with that derived from the use of a total spent dialysate collection technique. The partial spent dialysate collection method was used to harvest a small representative sample of the total spent dialysate. The volumes of spent dialysate collected by the partial and the total spent dialysate collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The total amount of urea nitrogen removed by dialysis as estimated by the partial spent dialysate collection method was similar to that determined by the total spent dialysate collection approach. As a result, the SRI value for urea obtained by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible to use a simple partial spent dialysate collection method to obtain SRI results in patients treated with hemodialysis.     

Increase in insulin antibodies during continuous subcutaneous insulin infusion and multiple-injection therapy in contrast to conventional treatment

Forty-five insulin-dependent diabetics were randomized to 1 yr treatment with either continuous subcutaneous insulin infusion (CSII), multiple insulin injections (MI), or continued conventional treatment. The CSII group used regular insulin only, the MI group used 4-6 premeal injections of regular insulin and intermediate insulin at night, and the conventional group used two daily injections of combined regular and intermediate insulin. Only highly purified porcine insulin was used. Near normoglycemia was obtained during CSII and MI but not during conventional treatment. Antibodies against insulin were measured in serum samples by measuring the binding of iodinated porcine insulin to serum after removal of free and antibody-bound insulin from the samples by acid charcoal. The percent binding of 125I-labeled insulin increased significantly during MI and CSII, in contrast to conventional treatment. Nineteen patients had sufficient binding capacity for Scatchard analysis. In the CSII and MI groups, high- or low-affinity antibodies or both were induced. When insulin was administered subcutaneously during MI or CSII for 1 yr, the insulin antibody production increased, in contrast with conventional treatment.     

Antivirals for the treatment of polyomavirus BK replication

Antiviral drugs with specific activity against polyomavirus replication have not been developed in the past. This deficiency has become fully apparent with the emergence of polyomavirus-associated nephropathy in kidney-transplant recipients, with a prevalence rate of up to 10%. In most cases, high BK virus replication in tubular epithelial cells causes significant cytopathology, leading to permanently impaired renal allograft function and return to hemodialysis within 6-60 months. In 5-10% of allogenic bone marrow/hematopoietic stem cell transplant recipients, high-level BK virus replication in the ureter/bladder mucosa has been associated with postengraftment hemorrhagic cystitis, which appears to involve significant immunopathology. Thus, in view of the increasing clinical need, a number of drugs have been studied in small case series. We review the antiviral strategies explored to date and specifically discuss available in vivo and in vitro data on cidofovir, leflunomide, fluoroquinolones and intravenous immunoglobulins, regarding mechanism, administration, dosing and outcome and provide a perspective on future therapy options.     

Improved postprandial glycaemic controls with insulin Aspart in type 2 diabetic patients treated with insulin

The effect on postprandial blood glucose control of an immediately pre-meal injection of the rapid acting insulin analogue Aspart (IAsp) was compared with that of human insulin Actrapid injected immediately or 30 before a test meal in insulin-treated type 2 diabetic patients with residual β-cell function. In a double-blind, double dummy crossover design, patients attended three study days where the following insulin injections in combination with placebo were given in a random order: IAsp (0.15 IU/kg body weight) immediately before the meal, or insulin Actrapid (0.15 IU/kg) immediately (Act-₀) or 30 minutes before (Act-₃₀) a test meal. We studied 25 insulin-requiring type 2 diabetic patients, including 14 males and 11 females, with a mean age of 59.7 years (range, 43–71), body mass index 28.3 kg/m² (range, 21.9–35.0), HbA_1c 8.5% (range, 6.8–10.0), glucagon-stimulated C-peptide 1.0 nmol/l (range, 0.3–2.5) and diabetes duration 12.5 years (range, 3.0–26.0). Twenty-two patients completed the study A significantly improved postprandial glucose control was demonstrated with IAsp as compared to Act₀, based on a significantly smaller postprandial blood glucose excursion (IAsp, 899 ± 609 (SD) mmol/l · min versus Act₀, 1102 ± 497 mmol/l min, p < 0.01) and supported by a significantly lower maximum serum glucose concentration (C_max) up to 360 min after dosing (IAsp, 10.8 ± 2.2 mmol/l vs. Act₀, 12.0 ±2.4 mmol/l, p < 0.02). No difference was demonstrated with a meal and Actrapid injected 30 minutes before the meal (AUC_glucose IAsp, 899 ± 609 mmol/l min vs. Act-₃₀, 868 ± 374 mmol/l min; C_max IAsp, 10.8 ± 2.2 mmol/l vs. Act-₃₀, 11.1 ± 1.8 mmol/l). No concerns about the safety of IAsp were raised. Immediate pre-meal administration of the rapid-acting insulin analogue Aspart in patients with type 2 diabetes resulted in an improved postprandial glucose control compared to Actrapid injected immediately before the meal, but showed similar control compared to Actrapid injected 30 minutes before the meal. These results indicate that the improved glucose control previously demonstrated with insulin Aspart compared to human insulin in healthy subjects and type 1 diabetic patients also applies to insulin-treated type 2 diabetic patients. Received: 3 December 1999 / Accepted in revised form: 3 March 2000