Cardiac autonomic dysfunction in young obese males is not associated with disturbances in pituitary-thyroid axis hormones.

OBJECTIVE: Obesity has been associated with hypothyroidism and cardiac autonomic dysfunction. The present study aimed to investigate whether cardiac autonomic dysfunction in young obese males might be related to an underlying thyroid disturbance. PATIENTS AND METHODS: On the basis of body mass index (BMI), 40 participants were grouped into normal weight group (NW; BMI = 18.5-25 kg/m(2); n = 15), over weight group (OW; BMI = 25-29.9 kg/m(2); n = 12) and obese group (OB; BMI ≥ 30 kg/m(2); n = 13). Electrocardiogram was recorded using PowerLab system and the time and frequency domain measures of heart rate variability (HRV) were calculated. Fasting blood samples were drawn for measurement of serum thyroid stimulating hormone (TSH), total thyroxin (TT4) and total triiodothyronine (TT3) concentrations. RESULTS: The levels of TSH, TT4 and TT3 were not significantly different between the groups. The frequency domain HRV parameter reflecting parasympathetic tone (high-frequency normalized units, HFnu) was significantly reduced in OB group. The parameters which reflect sympathetic activation (Heart rate, low-frequency normalized units; LFnu and the LF/HF ratio) were significantly increased in the OB group. HFnu was significantly and negatively correlated with BMI, waist hip ratio and body fat percentage, whereas LFnu and LF/HF ratio were significantly and positively correlated with the above mentioned parameters. No significant relationships were noted between the HRV parameters and the levels of TSH or thyroid hormones. CONCLUSIONS: Cardiac autonomic dysfunction in obese young adult males is not linked with underlying thyroid disturbance.

Long-term safety of fluticasone furoate nasal spray in adults and adolescents with perennial allergic rhinitis.

BACKGROUND: Fluticasone furoate is a novel-enhanced affinity glucocorticoid and its long-term safety must be assessed. This study was designed to assess the safety and tolerability of 12-month intranasal administration of fluticasone furoate in adult and adolescent patients with perennial allergic rhinitis (PAR). METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, 806 patients with PAR were randomized to once daily (od) fluticasone furoate nasal spray 110 microg (n = 605) or vehicle placebo nasal spray (n = 201) for 12 months, following a 7- to 14-day screening period. Safety was assessed by monitoring adverse events (AEs), 24-h urinary cortisol excretion, nasal and ophthalmic examinations, electrocardiograms and clinical laboratory tests. Plasma concentrations of fluticasone furoate were determined from blood samples. RESULTS: Fluticasone furoate was well tolerated. The incidence of most AEs was similar to that observed with placebo, with the exception of epistaxis, which was more frequently reported on active treatment. There were no clinically meaningful differences between fluticasone furoate and placebo in terms of safety assessments, including mean changes in ophthalmic parameters and 24-h urine cortisol excretion. Plasma concentrations of fluticasone furoate were not quantifiable in the majority of patients following intranasal administration. CONCLUSIONS: Long-term (12-month) administration of fluticasone furoate 110 microg od revealed an AE profile typical of the intranasal corticosteroid class in both adult and adolescent patients with PAR, with no evidence of clinically relevant systemic corticosteroid exposure.

Once daily fluticasone furoate nasal spray is effective in seasonal allergic rhinitis caused by grass pollen.

BACKGROUND: Fluticasone furoate is a new enhanced-affinity glucocorticoid with a unique combination of pharmacodynamic and physicochemical properties suitable for topical activity. METHODS: In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, patients [adults and adolescents >or=12 years of age with seasonal allergic rhinitis (SAR)] received once-daily (od) treatment for 2 weeks with either fluticasone furoate nasal spray 110 microg (n = 141) or placebo nasal spray (n = 144) administered in a unique, side-actuated device. Efficacy measures included total nasal symptom score (TNSS) and total ocular symptom score (TOSS). Patients also reported their overall response to therapy and rated their quality of life using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: Fluticasone furoate significantly improved the mean change from baseline in daily reflective TNSS compared with placebo (treatment difference of -1.757; P < 0.001). Fluticasone furoate was also significantly more effective in improving the morning predose instantaneous TNSS (treatment difference of -1.898; P < 0.001) and daily reflective TOSS (treatment difference of -0.741; P = 0.001). A significant treatment effect was observed as early as day 1. Compared with placebo-treated patients, fluticasone furoate-treated patients showed significantly greater improvements in overall evaluation of response to therapy (P < 0.001), as well as in overall RQLQ score (P < 0.001). Fluticasone furoate was well tolerated. CONCLUSION: Fluticasone furoate nasal spray 110 mug od was effective in improving the nasal symptoms of SAR. It also produced significant improvements in ocular symptoms.

Pathways of Nitrogen Metabolism in Nodules of Alfalfa (Medicago sativa L.).

Exposure of intact alfalfa nodules to (15)N(2) showed that in bacteroids the greatest flow of (15)N was to NH(3). Label was also detected in glutamic acid, aspartic acid, and asparagine (Glu, Asp and Asn), but at far lower levels. In the host plant cytosols, more (15)N was incorporated into Asn than into other compounds. Detached nodules were also used to study the metabolic pathway of N assimilation after exposure to (15)N(2) or vacuum infiltration with ((15)NH(4))(2)SO(4) in the presence or absence of different inhibitors of nitrogen assimilation: methionine sulfoximine (MSO), azaserine (AZA), or amino-oxyacetate (AOA). Treatment with MSO, an inhibitor of glutamine synthetase (GS), inhibited the flow of the label to glutamine (Gln)-amide, resulting in subsequently decreased label in Asnamide. Aza, which inhibits the formation of Glu from Gln by glutamate synthase (GOGAT), enhanced the labeling of the amide groups of both Gln and Asn, while that of Asn-amino decreased. When AOA was used to block the transamination reaction very little label was found in Asp and Asn-amino. The results are consistent with the role of GS/GOGAT in the cytosol for the assimilation of NH(3) produced by N(2) fixation in the bacteroids of alfalfa nodules. Asn, a major nitrogen transport compound in alfalfa, is mainly synthesized by a Gln-dependent amidation of Asp, according to feeding experiments using the (15)N-labeled amide group of glutamine. Data from (15)NH(4) (+) feeding support some direct amidation of Asp to form Asn.

Treatment and prophylaxis of disseminated Mycobacterium avium complex in HIV-infected individuals.

OBJECTIVE: To review the pathophysiology, epidemiology, treatment, and prophylaxis of disseminated Mycobacterium avium complex (MAC) infection in HIV-infected individuals. DATA SOURCES: A MEDLINE (January 1966-July 1997) and AIDSLINE (January 1980-July 1997) search of basic science articles pertinent to the MAC infection in HIV-infected patients. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: The organism, epidemiology, and pathophysiology of disseminated MAC are discussed for background. A review of clinical trials for the treatment and prophylaxis of disseminated MAC are presented, along with unresolved issues concerning these topics. CONCLUSIONS: The incidence of disseminated MAC has increased dramatically with the AIDS epidemic. The infection can lead to increased morbidity and mortality in HIV-infected patients. Treatment regimens for patients with a positive culture for MAC from a sterile site should include two or more drugs, including clarithromycin. Prophylaxis against disseminated MAC should be considered for patients with a CD4 cell count of less than 50/mm3.