Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: Biochemical rationale and case report

BACKGROUND: Glucosamine and chondroitin sulfate preparations are widely used as food supplements against osteoarthritis, but critics are skeptical about their efficacy, because of the lack of convincing clinical trials and a reasonable scientific rationale for the use of these nutraceuticals. Most trials were on osteoarthritis of the knee, while virtually no documentation exists on spinal disc degeneration. The purpose of this article is to highlight the potential of these food additives against cartilage degeneration in general, and against symptomatic spinal disc degeneration in particular, as is illustrated by a case report. The water content of the intervertebral disc is a reliable measure of its degeneration/ regeneration status, and can be objectively determined by Magnetic Resonance Imaging (MRI) signals. CASE PRESENTATION: Oral intake of glucosamine and chondroitin sulfate for two years associated with disk recovery (brightening of MRI signal) in a case of symptomatic spinal disc degeneration. We provide a biochemical explanation for the possible efficacy of these nutraceuticals. They are bioavailable to cartilage chondrocytes, may stimulate the biosynthesis and inhibit the breakdown of their extracellular matrix proteoglycans. CONCLUSION: The case suggests that long-term glucosamine and chondroitin sulfate intake may counteract symptomatic spinal disc degeneration, particularly at an early stage. However, definite proof requires well-conducted clinical trials with these food supplements, in which disc de-/regeneration can be objectively determined by MRI. A number of biochemical reasons (that mechanistically need to be further resolved) explain why these agents may have cartilage structure- and symptom-modifying effects, suggesting their therapeutic efficacy against osteoarthritis in general

Amiodarone therapy for drug-refractory fetal tachycardia.

Background - Fetal tachycardia complicated by ventricular dysfunction and hydrops fetalis carries a significant risk of morbidity and mortality. Transplacental digoxin is effective therapy in a small percentage, but there is no consensus with regard to antiarrhythmic treatment if digoxin fails. This study evaluates the safety, efficacy, and outcome of amiodarone therapy for digoxin-refractory fetal tachycardia with heart failure. Methods and Results - Fetuses with incessant tachycardia and either hydrops fetalis (n = 24) or ventricular dysfunction ( n = 2) for whom digoxin monotherapy and secondary antiarrhythmic agents ( n = 13) were not effective were treated transplacentally with a loading dose of oral amiodarone for 2 to 7 days, followed by daily maintenance therapy for <1 to 15 weeks. Digoxin therapy was continued throughout gestation. Newborns were studied by transesophageal pacing or ECG monitoring to determine the mechanism of tachycardia. Three fetuses were delivered urgently in tachycardia during amiodarone loading, and 3 required additional antiarrhythmic agents for sustained cardioversion. Amiodarone or amiodarone combinations converted 14 of 15 (93%) with reentrant supraventricular tachycardia, 2 of 2 with ventricular or junctional ectopic tachycardia, and 3 of 9 (33%) with atrial flutter. Amiodarone-related adverse effects were transient in 5 infants and 8 mothers. Mean gestational age at delivery was 37 weeks, with 100% survival. Conclusions - Orally administered amiodarone is safe and effective treatment for drug-refractory fetal tachycardia, specifically reentrant supraventricular tachycardia, junctional ectopic, or ventricular tachycardia, even when accompanied by hydrops fetalis or ventricular dysfunction

In vitro sealing ability of white and gray mineral trioxide aggregate (MTA) and white Portland cement used as apical plugs

This study evaluated the sealing ability of apical plugs made of white and gray MTA-Angelus® and white Portland cement placed via the root canal and having different thicknesses (2, 5 and 7 mm). Ninety extracted human single-rooted teeth were instrumented using a size 40 K-file to standardize the foraminal opening by the stepback technique. The teeth were assigned to 3 groups (n=30), according to the material used for fabrication of the apical plugs: A = gray MTA; B = white MTA; C = white Portland cement. The groups were subdivided into groups of 10 teeth each according to the apical plug thickness (2, 5 and 7 mm). Marginal apical dye leakage was assessed using 0.2% Rhodamine B solution in which the specimens were immersed for 72 hours at 37ºC. The roots were sectioned longitudinally in a buccolingual direction for apical plug exposure, and digital photographs were taken and analyzed by Image Tool image-analysis software. Data were analyzed statistically by Kruskal-Wallis and Dunn's tests. Significance level was set at 5%. The least percent leakage was observed for 5- and 7-mm-thick plugs (p<0.05). No significant difference (p>0.05) was found between gray MTA and white Portland cement. Among the three materials analyzed, white MTA presented the highest marginal leakage (p<0.05). The findings of the present study showed that gray MTA and Portland cement had better sealing ability than white MTA when used as apical plugs. Dye leakage was smaller for 5- and 7-mm-thick plugs compared to 2-mm-thick plugs

Multiple imputation of cognitive performance as a repeatedly measured outcome

BACKGROUND: Longitudinal studies of cognitive performance are sensitive to dropout, as participants experiencing cognitive deficits are less likely to attend study visits, which may bias estimated associations between exposures of interest and cognitive decline. Multiple imputation is a powerful tool for handling missing data, however its use for missing cognitive outcome measures in longitudinal analyses remains limited. METHODS: We use multiple imputation by chained equations (MICE) to impute cognitive performance scores of participants who did not attend the 2011-2013 exam of the Atherosclerosis Risk in Communities Study. We examined the validity of imputed scores using observed and simulated data under varying assumptions. We examined differences in the estimated association between diabetes at baseline and 20-year cognitive decline with and without imputed values. Lastly, we discuss how different analytic methods (mixed models and models fit using generalized estimate equations) and choice of for whom to impute result in different estimands. RESULTS: Validation using observed data showed MICE produced unbiased imputations. Simulations showed a substantial reduction in the bias of the 20-year association between diabetes and cognitive decline comparing MICE (3-4% bias) to analyses of available data only (16-23% bias) in a construct where missingness was strongly informative but realistic. Associations between diabetes and 20-year cognitive decline were substantially stronger with MICE than in available-case analyses. CONCLUSIONS: Our study suggests when informative data are available for non-examined participants, MICE can be an effective tool for imputing cognitive performance and improving assessment of cognitive decline, though careful thought should be given to target imputation population and analytic model chosen, as they may yield different estimands