Influence of pH on in vitro disintegration of phosphate binders

Hyperphosphatemia, a common complication in patients with end-stage renal disease, is treated with oral phosphate-binding medications that restrict phosphorus absorption from the gastrointestinal (GI) tract. Impaired product performance, such as failure to disintegrate and/or dissolve in the GI tract, could limit the efficacy of the phosphate binder. Disintegration may be as important as dissolution for predicting in vitro product performance for medications that act locally on the GI tract, such as phosphate binders. Furthermore, patients with end-stage renal disease have a wide range in GI pH, and pH can influence a product's performance. The purpose of this study was to determine the effect of pH on in vitro disintegration of phosphate binders. Fifteen different commercially available phosphate binders (seven calcium carbonate tablet formulations, two calcium acetate tablet formulations, three aluminum hydroxide capsule formulations, and three aluminum hydroxide tablet formulations) were studied using the United States Pharmacopeia (USP) standard disintegration apparatus. Phosphate binders were tested in simulated gastric fluid (pH 1.5), distilled water (pH 5.1), and simulated intestinal fluid (pH 7.5). Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within 30 minutes. Results indicate that 9 of the 15 phosphate binders tested showed statistically significant differences in disintegration time (DT) based on pH. The percentage of binders that passed the disintegration study test in distilled water, gastric fluid, and intestinal fluid were 80%, 80%, and 73%, respectively. The findings of this study show that the disintegration of commercially available phosphate binders is highly variable. The pH significantly affected in vitro disintegration in the majority of phosphate binders tested; how significantly this affects in vivo performance has yet to be studied.     

Comparing outcomes in renal replacement therapy: how should we correct for case mix?

The need to evaluate the effectiveness of clinical practice to justify expensive therapy in the face of financial constraints in all areas of health care delivery makes it necessary to identify groups of patients who are likely to benefit most from treatment. Various risk stratification methods have been used for analyzing survival probabilities for patients receiving renal replacement therapy. Complicated risk stratification methods produce large numbers of risk groups of small sizes, which makes comparison between individual centers difficult. We compared three simple methods of risk stratification, that divided patients into low-, medium-, and high-risk groups, in a cohort of 1,407 patients who commenced renal replacement therapy in five European countries during a 7-year period. Method 1 considered age (>55 years) and diabetes alone; method 2 used a higher age limit (>70 years) and comorbid illnesses, including those other than diabetes; and method 3 used only the number of comorbidities (none, 1, or > or =2) for stratification. Kaplan-Meier survival curves were constructed for comparison between risk groups and Cox's regression model used to assess strength of relationship with mortality. Although patient survival was significantly different between the low-, medium-, and high-risk groups using all three methods, Cox's regression analysis showed that method 2 provided the greatest discrimination between risk groups. In predicting mortality, method 2 (based on comorbidities and age) showed the highest sensitivity and specificity (84% and 80%, respectively) compared with method 1 (80% and 74%) and method 3 (64% and 82%). Validation of this approach in other populations in a prospective study is required before this method, which takes into account the influences of both age and comorbidity for risk stratification, can be used for comparing survival data and for presenting results of renal replacement therapy.     

Novel lectins from rhizomes of two Acorus species with mitogenic activity and inhibitory potential towards murine cancer cell lines

Two novel lectins were purified from rhizomes of two sweet flag species, namely Acorus calamus (Linn.) and Acorus gramineus (Solandin Ait.) by affinity chromatography on mannose linked epoxy-activated Sepharose 6B. The apparent molecular mass of the lectins, as determined by gel filtration chromatography, was 56 kDa for ACL and 55 kDa for AGL. In SDS-PAGE, pH 8.3, both lectins migrated with a subunit molecular mass of 13.6 kDa and 13.5 kDa, respectively, under reducing and non-reducing conditions thus indicating the absence of disulphide linkages. Acorus lectins readily agglutinated rabbit, rat and guinea pig erythrocytes. Both ACL and AGL also reacted with RBCs from sheep, goat and human ABO blood groups after neuraminidase treatment. ACL and AGL were inhibited by mannose/glucose and their derivatives. The most effective inhibitor was methyl-alpha-D-mannopyranoside. Acorus lectins were stable up to 55 degrees C, did not require metal ions for their activity and were also affected by high concentrations of denaturants like urea, thiourea and guanidine-HCl. These lectins showed potent mitogenic activity towards mouse splenocytes and human lymphocytes. Both ACL and AGL also significantly inhibited the growth of J774, a murine macrophage cancer cell-line and to lesser extent WEHI-279, a B-cell lymphoma.     

Office management of the adolescent with diabetes mellitus

Diabetes mellitus (DM) is a chronic metabolic disorder caused by absolute or relative insulin deficiency. It causes disturbances in carbohydrate, protein, and fat metabolism. Environmental triggers superimposed on a genetic predisposition are responsible for the clinical expression of the syndrome. This article outlines current ideas in diagnosis and treatment of diabetes in adolescents. The"team approach" to outpatient diabetes management is described,with the hope that it will be of benefit to primary care physicians and their office staff. Advances in diabetes care regimens, and tools used in diabetes care are briefly summarized. Summary tables are provided to assist in routine care, troubleshooting, and advanced management.     

Cannabidiol enhances consolidation of explicit fear extinction in humans

Rationale

Whilst Cannabidiol (CBD), a non-psychotomimetic cannabinoid, has been shown to enhance extinction learning in rats, its effects on fear memory in humans have not previously been studied.

Objectives

We employed a Pavlovian fear-conditioning paradigm in order to assess the effects of CBD on extinction and consolidation.

Method

Forty-eight participants were conditioned to a coloured box (CS) with electric shocks (UCS) in one context and were extinguished in a second context. Participants received 32 mg of CBD either following before or after extinction in a double-blind, placebo-controlled design. At recall, 48 h later, participants were exposed to CSs and conditioning contexts before (recall) and after (reinstatement) exposure to the UCS. Skin conductance and shock expectancy measures of conditioned responding were recorded throughout.

Results

Successful conditioning, extinction and recall were found in all three treatment groups. CBD given post-extinction enhanced consolidation of extinction learning as assessed by shock expectancy. CBD administered at either time produced trend level reduction in reinstatement of autonomic contextual responding. No acute effects of CBD were found on extinction.

Conclusions

These findings provide the first evidence that CBD can enhance consolidation of extinction learning in humans and suggest that CBD may have potential as an adjunct to extinction-based therapies for anxiety disorders.     

Intraoperative floppy iris syndrome in Indian population: A prospective study on incidence,risk factors,and impact on operative performance

Purpose:

The purpose of this study was to evaluate the incidence, risk factors, and impact of intraoperative floppy iris syndrome (IFIS) on surgical performance.

Materials and Methods:

Consecutive cataract surgeries from October 2010 to Feb 2011 (1003 eyes, 980 patients; 568 males, 412 females) were analyzed prospectively. Operating surgeon, masked about medication history, noted the intraoperative details. Cases were identified as IFIS or non-IFIS. Multivariate analysis was performed to find risk factors for IFIS.

Results:

Prevalence of tamsulosin use among men undergoing cataract surgery was 7.0% (41) with incidence of IFIS 4.78% (48). On multivariate analysis, hypertension (OR: 3.2, 95% confidence interval, 95% CI: 1.39-6.57; P = 0.005), use of tamsulosin (OR: 133.32, 95% CI: 50.43-352.48; P < 0.0001), or alfuzosin (OR: 9.36, 95% CI: 2.34-37.50; P = 0.002) were the factors associated with IFIS. Among men taking tamsulosin (n = 41) and alfuzosin (n = 28), 68.3% and 16.6% developed IFIS, respectively. In subgroup analysis of men on tamsulosin, no factor added to the risk posed by tamsulosin. Seventeen of 944 eyes not exposed to any drug had IFIS (0.018%). On subgroup analysis, only risk factor for IFIS was hypertension (OR: 4.67, 95% CI: 1.63-13.35; P = 0.002). Of 48 IFIS eyes, the surgeon observed increased difficulty in 57.1% (21) and additional measures were required in 9 eyes. Mean operative time was increased in IFIS eyes (11.68 ± 3.46 vs. 10.01 ± 0.22 min; P = 0.001). Surgical outcome was good in all cases.

Conclusion:

The prevalence of tamsulosin intake and IFIS incidence is higher in India. Current tamsulosin/alfuzosin use and hypertension are important risk factors. IFIS makes the surgery more difficult, significantly prolongs the operative time, and predisposes for other intraoperative complications. However, with appropriate management, final operative outcome is not affected.     

Relationship of Psychosocial Risk Factors, Certain Personality Traits and Myocardial Infarction in Indians: A Case�Ccontrol Study

Objective:

To investigate the relationship of psychosocial factors (lack of social support, stress and subjective well-being) and personality traits with myocardial infarction (MI).

Materials and Methods:

A case–control study involving 100 cases and 100 matched controls was conducted in Lok Nayak Hospital, New Delhi.

Results:

Stress over 1 year was significantly higher in cases (P < 0.001). However, difference was not significant when scores of social support (P = 0.2), Presumptive Stressful Life Event (PSLE) over lifetime (P = 0.058) and subjective well-being (P = 0.987) were compared. MI was significantly associated with hyperactive (P < 0.001), dominant (P = 0.03), egoistic (P < 0.001) and introvert (P < 0.001) personalities.

Conclusion:

Certain personality traits and recent stress may be important risk factors of MI, especially in Indians. The finding may have implications on the preventive strategies planned for MI patients.