Safety of Selective COX-2 Inhibitors in Aspirin/Nonsteroidal Anti-inflammatory Drug-Intolerant Patients: Comparison of Nimesulide, Meloxicam, and Rofecoxib

Background. Intolerance to acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) is a crucial problem in clinical practice. There is, therefore, a need for safer NSAIDs in patients with analgesic intolerance. Objective. To assess the safety of nimesulide, meloxicam, and rofecoxib, selective COX-2 inhibitors, in a group of ASA/NSAIDs-intolerant patients. Method. Tolerances to nimesulide, meloxicam, and rofecoxib were assessed by single-blind placebo-controlled oral challenges. One hundred twenty-seven subjects with history of adverse reaction to ASA/NSAIDs received oral challenges with nimesulide, 61 subjects were challenged with meloxicam, 51 subjects were challenged with rofecoxib, and 37 subjects were challenged with all three drugs. Placebos were given to all patients on the first day of the study. On the second day, one-fourth and three-fourths of the therapeutic doses of the active drugs (nimesulide 100 mg, meloxicam 7.5 mg, or rofecoxib 25 mg) were given at 60-minute intervals. There was at least a 3-day interval between challenge tests. Erythema, pruritus accompanied by erythema, urticaria/angioedema, rhinorrhea, nasal obstruction, sneezing, dyspnea, or cough associated with a decrease of at least 20% in the forced expiratory volume (FEV₁) and hypotension were considered as positive reactions. Results. Positive reactions to the nimesulide, meloxicam, and rofecoxib challenges were observed in 18/127 (14.3%), 5/61 (8.1%), and 1/51 (2.0%) patients, respectively. In each group of nine patients, there were two patients with asthma and four who developed skin type reactions and asthmatic reactions, respectively, to the nimesulide challenge. Among five patients who reacted to the meloxicam challenge, asthmatic type reactions were detected in two asthmatics. Only one urticarial type reaction was observed with rofecoxib challenge in one patient who presented with anaphylaxis to ASA/NSAIDs. All patients with asthma tolerated rofecoxib without any adverse effects. None of the patients reacted to the placebo. Among 37 patients challenged with all three drugs, 11 reacted to nimesulide, and one patient reacted only to meloxicam. Three patients reacted to more than one of the drugs tested, and one of them reacted to all drugs. Conclusion. This is the first placebo-controlled report comparing these three drugs. The results indicate that among these alternative drugs for ASA/NSAIDs-intolerant patients, rofecoxib seems to have the most favorable tolerability.     

A new reference method for the validation of the nutrient profiling schemes using dietary surveys

Nutrient profiles of foods are increasingly used as the scientific basis of nutritional labeling, health claims, or nutritional education. Nutrient profiling schemes are based on sets of rules, scores, or thresholds applied to the nutritional composition of foods. However, there is a lack of scientific validation of nutritional profiling schemes. To develop a reference method using existing dietary surveys, to define a set of indicator foods that are positively or negatively associated with a "healthy diet." Such indicator foods can be used both for establishing relevant nutrient profiles and for the validation of existing or future nutrient profiling schemes. The proposed validation method is based on food and nutrient intakes of adults participating in national dietary surveys in five EU countries: Belgium (n = 2,507), Denmark (n = 3,151), France (n = 1,474), Ireland (n = 1,379), and Italy (n = 1,513). The characterization of indicator foods is divided in two steps. First, "healthy diets" of individuals are identified in the five national dietary surveys by comparison to the Eurodiet reference intakes. Second, indicator foods associated positively or negatively to the "healthy diets" are determined. With a P-value of 10(-3) for the test of comparison of food intakes between the "most healthy eaters" and the "less healthy eaters," it was possible to identify 294 indicator foods out of 1,669 foods tested in the five countries. In all the countries except Italy, there were more indicator foods positively associated than indicator foods negatively associated with the "healthy diet." The food categories of these indicator foods were in good agreement with Food Based Dietary Guidelines like the USDA dietary guideline for Americans. A new reference method for the validation of profiling schemes was developed based on dietary intake data from using dietary surveys in five European countries. Only a minority of foods consumed in these dietary surveys could be used as indicator foods of healthy or unhealthy diets in order to subsequently test nutritional profiling schemes. Further work is needed to build a list of indicator foods that could be considered as a "gold standard."     

Comparison of different nutrient profiling schemes to a new reference method using dietary surveys

A new EU regulation on nutrition and health claims made on foods has entered into force in January 2007. The regulation provides for the use of nutrient profiles to determine which foods may bear claims but does not specify what the profiles should be or how they should be developed. Several nutrient profiling schemes have already been established. Therefore, it is necessary to develop approaches to test if the existing profiling schemes could fulfil the new regulation needs. The aim of the present study is to investigate how reference "indicator foods" derived from national dietary surveys in five different countries, are classified according to three existing nutrient profiling schemes: The UK Food Standards Agency (FSA) model, The Dutch Tripartite classification model and the US FDA model used for regulating health claims. "Indicator foods" that have been shown to be positively or negatively associated with healthy diets in adults in five EU countries were classified according to each of the three profiling schemes. The performance and effectiveness of each profiling scheme in correctly classifying the "indicator foods" were assessed using sensitivity and specificity ratios. The sensitivity and the specificity ratios of the three profiling schemes tested were relatively good. There were only small differences of performance between the three systems. A significant negative correlation between sensitivity and specificity was observed. The level of concordance between the classification of the "indicator foods" that have been selected because of being positively or negatively associated with a healthy diet and the classification by each of the three profiling methods tested was quite good. However, further improvement of the "indicator foods" approach is needed if it is to serve as a "gold standard".     

Effect of stimulation of the spinal cord on phasic and tonic reflexes in patients with central motor neuron damage

Spinal cord stimulation (SCS) is a method enabling the control of increased muscle tonus to be achieved in various spinal cord injuries. Polyelectromyographic (PEMG) methods were used for neurophysiological assessment of the degree of cord damage and persistent spinal reflexes as well as supramedullary influences. The analysed material comprised 40 PEMG records in 19 patients with spastic paraparesis or paraplegia after cord injury, cord tumour or multiple sclerosis. In 15 cases tentative epidural cord stimulation was done and 11 patients received implantation of a system for long-term stimulation. In most cases the epidural electrodes were implanted below the damaged segment, usually in the thoracic part of the cord. Before and after SCS beginning PEMG was done with a 16-channel Mingograph Siemens Elema with simultaneous recording of the responses from the symmetric muscles: quadriceps, semitendinous, adductor femoris, anterior tibialis and triceps surae. The effect of SCS was analysed on exteroceptive and proprioceptive reactions during testing of knee and ankle reflexes, and on the response of the muscles to vibration. In most patients a reduction was observed of the intensity of tendon reflexes, particularly the spread of the reflex to the contralateral extremity was no longer seen. The vibration reflex had a tonic character persisting in 48% of the studied muscles, even in patients with clinically complete transsection of the cord. The change of the character of monosynaptic reflexes and the presence of the vibration reflex suggest that SCS modifies the proprioceptive segmental spinal reactions.     

Intestinal bifidobacteria that produce trans-9, trans-11 conjugated linoleic acid: a fatty acid with antiproliferative activity against human colon SW480 and HT-29 cancer cells

Bifidobacterium breve species of human intestinal origin have the ability to synthesize cis-9, trans-11 (c9, t11) conjugated linoleic acid (CLA) from free linoleic acid. In this study, the ability of Bifidobacterium species to isomerize C(18) polyunsaturated fatty acids was investigated, and the antiproliferative activities of the two main microbially produced CLA isomers were assessed. Linoleic acid was converted principally to c9, t11 CLA and lesser amounts of t9, t11 CLA, whereas c9, t11 CLA was converted mainly to t9, t11 CLA. Likewise, t10, c12 CLA was converted principally to t9, t11 CLA, which was incorporated into the bacterial cell membranes. To examine the antiproliferative effect of the two main CLA isomers formed, SW480 and HT-29 human colon cancer cells were cultured in the presence of c9, t11 CLA and t9, t11 CLA. The t9, t11 CLA had a more potent antiproliferative effect than c9, t11 CLA. It is tempting to suggest that the ability of Bifidobacterium to produce such bioactive metabolites may be associated with the beneficial effects of bifidobacteria present in the human gastrointestinal tract.     

Aggressive variants of papillary thyroid carcinoma

A number of histologic variants of well‐differentiated papillary carcinoma have been found to be associated with more aggressive tumor behavior. Tall cell, columnar cell, diffuse sclerosing, solid/trabecular, and insular variants of well‐differentiated papillary thyroid cancer are all potentially more aggressive than conventional papillary thyroid cancer. When subjected to multivariate analysis, however, evidence that the histologic subtype of tumor is an independent predictor of outcome is weak. Rather, the aggressive variants tend to present with features recognized by other staging systems as associated with a worse prognosis, including higher histologic grade, extracapsular spread, large tumor size, and the presence of distant metastases. Prognosis is directly related to the presence of these features. The state of our knowledge is limited by the relatively small number of cases that have been studied. The presence of an aggressive variant of papillary carcinoma should alert the surgeon that he is dealing with a potentially aggressive tumor. Clinical treatment decisions should be based on the stage of the disease, influenced by the knowledge that the aggressive variants tend to be associated with higher risk factors. The surgeon must be prepared to perform at the first, or second stage, a total thyroidectomy, central compartment neck dissection, additional lymphadenectomy, and/or resection of invaded surrounding structures, and search for distant metastasis. Postoperative radioactive iodine should generally be administered for these variants as they will generally be intermediate to advanced tumors. The tall cell variant is often refractory to such treatment but may be susceptible to treatment targeted against BRAF mutation. External beam irradiation may be used in cases of incomplete resection. © 2010 Wiley Periodicals, Inc. Head Neck, 2011     

Central compartment dissection in laryngeal cancer

We report here a review of the literature intended to clarify the nomenclature and boundaries of the nodes in the “central compartment” of the neck, the frequency with which tumors from the different laryngeal sites metastasize to these nodes, and the indications for central compartment node dissection in the treatment of cancers of the larynx. From this review, we conclude that, until consensus is reached about grouping of the lymph nodes in this area, it is best to refer to these nodes by their anatomic location, ie, prelaryngeal, pretracheal, or paratracheal lymph nodes. It is also advisable to describe dissection of these nodes as selective neck dissection (SND) with an annotation about the specific lymph node groups removed. Metastases in prelaryngeal and paratracheal lymph nodes in patients with squamous cell carcinoma of the larynx are associated with increased tumor recurrence, more frequent metastases in lymph nodes of the lateral compartment of the neck, and decreased survival. If untreated, they may lead to the development of peristomal recurrence. Therefore, elective treatment of level VI nodes is recommended in patients with squamous cell carcinomas of the subglottic region, advanced glottis carcinomas with subglottic extension, and in certain advanced carcinomas of the supraglottic region. © 2010 Wiley Periodicals, Inc. Head Neck, 2011