The use of heart rate variability in assessing precompetitive stress in high-standard judo athletes.

The objective of this study is to examine the sensitivity to and changes in heart rate variability (HRV) in stressful situations before judo competitions and to observe the differences among judo athletes according to their competitive standards in both official and unofficial competitions. 24 (10 male and 14 female) national- and international-standard athletes were evaluated. Each participant answered the Revised Competitive State Anxiety Inventory (CSAI-2R) and their HRV was recorded both during an official and unofficial competition. The MANOVA showed significant main effects of the athlete's standard and the type of competition in CSAI-2R, in HRV time domain, in HRV frequency domain and in HRV nonlinear analysis (p<0.05). International-standard judo athletes have lower somatic anxiety, cognitive anxiety, heart rate and low-high frequency ratio than national-standard athletes (p<0.05). International-standard athletes have a higher confidence, mean RR interval, standard deviation of RR, square root of the mean squared difference of successive RR intervals, number of consecutive RR that differ by more than 5 ms, short-term variability, long-term variability, long-range scaling exponents and short-range scaling exponent than national-standard judo athletes. In conclusion, international-standard athletes show less pre-competitive anxiety than the national-standard athletes and HRV analysis is sensitive to changes in pre-competitive anxiety.

Occurrence of Chlamydia trachomatis and Chlamydia pneumoniae in paediatric respiratory infections.

An emerging body of evidence suggests that half of asthma in both children and adults is associated with chronic lung infection. The aim of the present study was to determine the frequency of viable Chlamydia pneumoniae (Cp) and C. trachomatis (Ct) in the respiratory tracts of paediatric patients with chronic respiratory diseases. Bronchoalveolar lavage fluid (BALF) samples obtained from 182 children undergoing bronchoscopy for clinical reasons were assayed using PCR analysis, in vitro tissue culture and immunofluorescence staining for the presence of Cp and Ct. Chlamydia-specific DNA was detected by PCR in 124 (68%) out of 182 patients; 79 were positive for Cp, 77 positive for Ct and 32 for both organisms; 75 patients had cultivable Chlamydia. Ct DNA prevalence decreased, whereas Cp positivity generally increased with age. A total of 59 out of 128 asthma patients and 16 out of 54 nonasthmatics were Chlamydia culture positive. When the patients were divided into inflammatory versus noninflammatory airway disease, there were 69 (46%) out of 150 and six (18%) out of 32 BALF samples with cultivable Chlamydia, respectively. Viable Chlamydia pneumoniae and Chlamydia trachomatis occur frequently in children with chronic respiratory diseases and may be more prevalent in asthma patients. To the current authors' knowledge, this is the first report of viable Chlamydia trachomatis in the lungs of children.

Safety of endobronchial biopsy in 170 children with chronic respiratory symptoms.

BACKGROUND: There is a paucity of bronchial biopsy data in children. A major limitation is concern over the safety of the procedure. This paper reports the results of efforts to develop a method that is safe and provides adequate specimen for evaluation. METHODS: 170 children aged 2.5 to 16 years with chronic respiratory symptoms were studied under general anaesthesia in an outpatient surgery setting. Bronchoalveolar lavage and biopsies were obtained using a 4.9 mm flexible bronchoscope through a laryngeal mask airway. At least three bioipsies were taken. RESULTS: No patient required topical adrenaline to control bleeding, nor was there a change in the state of any of the patients. There were no episodes of pneumothorax, haemoptysis, pneumonia, or significant fever. All children less than four years old received a single dose of antibiotic intravenously after the procedure. The average length of time for the procedure was 12 minutes (range 6 to 27). Recovery time averaged 90 minutes. The limiting factor was the ability of the child's airway to accomodate the bronchoscope. CONCLUSIONS: This report should encourage clinicians to incorporate endobronchial biopsy into the evaluation of children with difficult respiratory problems.

Tolerability and safety of 0.1% diclofenac plus 0.3% tobramycin fixed-dose ophthalmic solution: a randomized, comparative, controlled study in healthy volunteers.

The purpose of this double-blind, observer-masked, randomized, crossover trial was to compare the tolerability and safety of a fixed-dose ophthalmic solution of 0.3% tobramycin plus 0.1% diclofenac versus Tobrex (tobramycin sulfate ophth) and Voltaren (diclofenac sodium). Control treatments included a saline solution and a control solution of 0.3% tobramycin prepared by Alcon Cusí. Ten healthy volunteers received three consecutive instillations of 1 drop of a given ophthalmic solution at 08:00, 11:00 and 14:00 h to the same eye; after a washout period of 18 h, the next ophthalmic solution was tested according to a randomized sequence. Occurrence, intensity, and duration of ocular irritation and conjunctival hyperemia at baseline and after the three instillations were recorded. Slit lamp biomicroscopy examination, measurement of intraocular pressure (IOP) changes, visual acuity, and examination of the fundus of the eye were performed after each third instillation by an ophthalmologist. Side effect incidence and patient and investigator opinions were also recorded. Results showed that Voltaren instillation induced statistically significant ocular irritation (p = 0.0077); the remaining ophthalmic solutions tested caused no ocular irritation (Physiological Saline Braun, p = 0.9808; Tobrex, p = 0.8826; control 0.3% tobramycin solution, p = 0.8327; and 0.1% diclofenac plus 0.3% tobramycin, p = 0.5399). None of the ophthalmic solutions tested caused severe conjunctival hyperemia. Analysis of the sum of conjunctival parameters of both eyes for all ophthalmic solutions studied showed no statistically significant differences (p = 0.4688). Moderate superficial punctate keratitis was observed after instillation of Voltaren and of 0.1% diclofenac plus 0.3% tobramycin (1 subject each) that spontaneously resolved within 2 days. Slit lamp biomicroscopy, visual acuity and IOP values showed no statistically significant changes. No systemic side effects related to the study treatments were recorded. In conclusion, the ophthalmic solution containing 0.1% diclofenac plus 0.3% tobramycin was well tolerated under the study conditions. Its tolerability was equivalent to that of Braun physiological saline, Tobrex and a control 0.3% tobramycin solution and was better than that of Voltaren.

[Transesophageal cardiac echography and paracardiac tumor masses. Apropos of a case]. / Echographie cardiaque transoesophagienne et masses tumorales paracardiaques. A propos d'un cas.

Computed tomography is currently the reference examination in the investigation of mediastinal tumours. We report a case of pericardial tumour revealed by transoesophageal echocardiography. This investigation immediately defined the limits of this mass and its relations with cardiac cavities and large vessels and suggested the main features of its tissue structure. However, the aetiological diagnosis is still based on CT-guided needle biopsy or investigation by mediastinoscopy or thoracotomy. Our case consisted of a non-Hodgkin lymphoma. Transoesophageal echocardiography is a non-irradiating technique, which can be performed at the patient's bed and which allows a precise assessment of the pericardial regions, especially the right pericardial regions.

Pharmacological properties of hirudin and its derivatives. Potential clinical advantages over heparin.

Hirudin and its derivatives represent the first parenteral anticoagulants introduced since the discovery of heparin in the early 1900s. Hirudin, the naturally occurring anticoagulant of the leech, is a single peptide chain of 65 amino acids with a molecular weight of about 7000. Recombinant technology has developed methods to produce recombinant forms of hirudin (r-hirudin) in sufficient quantities for therapeutic use. Hirudin is a potent thrombin-specific inhibitor that forms equimolar complexes with thrombin. It represents a new anticoagulant agent in a field in which heparin has been the only available drug for many years. In contrast to heparin, hirudin does not require antithrombin III as a cofactor, is not inactivated by antiheparin proteins, has no direct effects on platelets and may also inactivate thrombin bound to clot or the subendothelium. In humans, experience with r-hirudin in preventing or treating venous thromboembolism is very preliminary. However, r-hirudin achieved promising results in patients with unstable angina, or following coronary angioplasty. In patients with acute myocardial infarction, 3 important clinical trials were stopped because of an excess of bleeding complications. At present, the discovery of a r-hirudin regimen that is more efficacious than heparin and at least as safe needs a reappraisal of the drug in further trials.

TNF-alpha, IL-8, soluble ICAM-1, and neutrophils in sputum of cystic fibrosis patients.

The cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and intercellular adhesion molecule-1 (ICAM-1) have important roles in regulating neutrophil migration and the inflammatory response. To determine whether the concentration of these cytokines and soluble ICAM-1 (sICAM-1) in sputum was increased in patients with cystic fibrosis during acute exacerbations, we conducted (1) a cross-sectional study of 40 patients, 22 who were clinically well and 18 with acute pulmonary exacerbations; and (2) an 11 months longitudinal study of 16 patients. Significant differences in clinical scores, pulmonary function, and sputum neutrophil density were found between the acutely ill and the well group. There was a strong linear relationship (P < 0.0005) between TNF-alpha and IL-8 concentrations in sputum, but no association between clinical status and cytokine concentrations. The concentration of sICAM-1 was lower in acutely ill compared with well patients in the cross-sectional study. Recovery of exogenous IL-8 added to sputum was complete, while recovery of TNF-alpha averaged 70%. Recovery of exogenous sICAM-1 was only 43%, and the recoveries were lower in sputum samples from acutely ill patients than those from stable patients (P = 0.018). These data indicate that in cystic fibrosis patients, sputum concentrations of TNF-alpha and IL-8 are not increased during acute exacerbations of pulmonary inflammation.

Ex vivo antibacterial properties of rufloxacin compared with those of norfloxacin in a study with healthy volunteers.

Twelve adult males participated in a randomized crossover phase I clinical trial comparing serum bactericidal titers (SBTs), urine bactericidal titers (UBTs), and urine killing rates (UKRs) against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, after the administration of single 400-mg doses of rufloxacin and norfloxacin at different times up to 72 h postdose. SBTs were significantly higher (P < 0.05) against E. coli from 8 to 48 h and against S. aureus from 4 to 24 h with rufloxacin. UBTs for E. coli were higher (P < 0.05) for norfloxacin at early sample times (0 to 8 h) but higher for rufloxacin (P < 0.05) at sample times from 16 h on for both E. coli and S. aureus. Similar UKRs were obtained for both quinolones for 0 to 2 h and 8 to 12 h, but the UKR was maintained for 72 h with rufloxacin. The high and sustained mean levels of rufloxacin in urine (> 35 micrograms/ml), median UBTs (> 32 for E. coli and 16 for S. aureus) and UKRs for E. coli suggest prolonged urine antibacterial activity (for at least 72 h) and its use as a single 400-mg dose in the treatment of uncomplicated cystitis.

Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications.

Zolpidem is an imidazopyridine which differs in structure from the benzodiazepines and zopiclone. It is a strong sedative with only minor anxiolytic, myorelaxant and anticonvulsant properties, and has been shown to be effective in inducing and maintaining sleep in adults. The available evidence suggests that zolpidem produces no rebound or withdrawal effects, and patients have experienced good daytime alertness. Zolpidem 10mg in non-elderly and a reduced dose of 5mg in elderly individuals are clinically effective. In humans, the major metabolic routes include oxidation and hydroxylation; none of the metabolites appears to be pharmacologically active. The pharmacological activity of zolpidem results from selective binding to the central benzodiazepine receptors of the omega 1 subtype. Zolpidem is approximately 92% bound to plasma proteins; absolute bio-availability of zolpidem is about 70%. After single 20mg oral doses, typical values of pharmacokinetic variables for zolpidem in humans are: a peak plasma concentration of 192 to 324 micrograms/L occurring 0.75 to 2.6 hours postdose; a terminal elimination half-line of 1.5 to 3.2 hours; and total clearance of 0.24 to 0.27 ml/min/kg. Zolpidem pharmacokinetics are unchanged during multiple-dose treatment. Zolpidem pharmacokinetics are not significantly influenced by gender. Clearance of zolpidem in children is 3 times higher than in young adults, and is lower in very elderly people. There are no significant differences in the pharmacokinetic parameters between various racial groups. Dosage reduction appears to be prudent in patients with renal disease, and caution should be exercised when prescribing zolpidem to elderly patients with hepatic impairment. Coadministration of haloperidol, cimetidine, ranitidine, chlorpromazine, warfarin, digoxin or flumazenil do not alter the pharmacokinetics of zolpidem; flumazenil predictably antagonises the hypnotic effects of zolpidem. Alertness tends to be reduced when cimetidine is combined with zolpidem. Volunteers treated with imipramine plus zolpidem developed anterograde amnesia.

Comparison of rufloxacin and norfloxacin effects on faecal flora.

The suppression of faecal Escherichia coli by quinolones was studied in a randomized cross-over phase I trial with single oral doses of 400 mg rufloxacin or norfloxacin. Both drugs caused > 70% decontamination in a similar number of subjects in the 72 h post-dose period (83% vs 100% respectively), but suppression of E. coli at 168 h was significantly (P < 0.05) higher after rufloxacin (83.3 vs 40%).

Epidemiologic study of an outbreak of clenbuterol poisoning in Catalonia, Spain.

In an investigation of 113 cases of clenbuterol poisoning in Catalonia, Spain, in 1992, more than 50 percent of those affected were found to have had symptoms of nervousness, tachycardia, muscle tremors, myalgia, and headache. There was no significant difference in the distribution of symptoms according to sex (P = 0.97). The period of incubation varied between 15 minutes and 6 hours and the duration of symptoms between 90 minutes and 6 days. Clenbuterol was detected in 47 urine samples in amounts ranging from 11 to 486 parts per billion. No traces of clenbuterol were found in serum samples. Intoxication occurred in association with the ingestion of veal liver, irrespective of the way in which the liver had been cooked. The association between consuming liver and falling ill was statistically significant (P < 0.0001). In one family, the suspected source of intoxication was meat (veal tongue) and in another canneloni. None of the patients died as a result of the intoxication. The findings reinforce the need to uphold the prohibition of the use of clenbuterol in cattle farming in those countries and communities where it already exists and to contemplate a stricter regulation of its therapeutic use.

Repeated dose pharmacokinetics of pancopride in human volunteers.

The aim of this study was to assess the pharmacokinetic profile of pancopride after repeated oral dose administration of 20 mg pancopride in tablet form once a day for 5 d in 12 healthy male volunteers. Plasma levels were measured by HPLC using a solid phase extraction method and automated injection. The minimum quantification limit of pancopride in plasma was 2 ng mL-1. The maximum plasma concentration (mean +/- SD) after the first dose was 92.5 +/- 41.5 ng ML-1 and tmax was 1.7 +/- 0.9 h. The elimination half-life (t1/2) was 14.3 +/- 6.9 h. The area under the concentration-time curve from zero to infinity (AUC) was 997 +/- 396 ng h mL-1. The maximum plasma concentration (mean +/- SD) at steady state (day 5) was 101.8 +/- 36.9 ng mL-1 and tmax was 2.2 +/- 1.2 h. The elimination half-life (t1/2) was 16.3 +/- 2.7 h and the minimum plasma concentration (Cssmin) was 16.6 +/- 6.9 ng mL-1. The area under the concentration-time curve during the dosing interval (AUCss tau) was 995 +/- 389 ng h mL-1. The average plasma concentration at steady state (Cssav) was 43.3 +/- 16.1 ng mL-1 and the experimental accumulation ratio (RAUC) was 1.34 +/- 0.19, whereas the mean theoretical value (R) was 1.40 +/- 0.29. The results obtained showed a good correlation between the experimental plasma levels and the expected values calculated using a repeated dose two-compartment model assessed by means of the Akaike value. It is concluded that the pharmacokinetics of pancopride are not modified after repeated dose administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of alfuzosin after single oral administration to healthy volunteers, of three different doses.

The aim of this study was to assess the linearity of pharmacokinetic of alfuzosin, administered by oral route, at the doses of 1, 2.5, and 5 mg to 12 young healthy volunteers. The pharmacokinetic parameters (tmax, Cmax, AUC, t1/2 beta) obtained from plasma alfuzosin concentrations after administration of the three doses show that pharmacokinetics of alfuzosin is linear in the range of doses 1-5 mg. Mean pharmacokinetic parameters of alfuzosin observed after 1, 2.5, and 5 mg were, respectively: tmax (h) 1.5 +/- 0.3, 1.1 +/- 0.2, 1.3 +/- 0.1; Cmax (ng ml-1) 2.6 +/- 0.3, 9.4 +/- 1.2, 13.5 +/- 1.0; AUC (ng ml-1 h) 17.7 +/- 2.9, 51.7 +/- 7.1, 99.0 +/- 14.1; t1/2 (h) 3.7 +/- 0.4, 3.9 +/- 0.2, 3.8 +/- 0.3. Cmax (corrected by the dose) obtained after 2.5 mg was significantly higher than those obtained after 1 and 5 mg. This difference seems to be due principally to the intraindividual variability. The absence of statistically significant difference on individual values of AUC corrected by the administered dose, supports the linearity of the pharmacokinetics of alfuzosin in the range of doses between 1 and 5 mg. Some postural hypotension, clinical criterion, was observed with a frequency increasing with the dose in these healthy subjects: 0 volunteers of 12 after 1 mg, 3 volunteers of 12 after 2.5 mg and 4 volunteers of 12 after 5 mg.

Anabolic steroids: interest among parents and nonathletes.

To determine the nature and extent of public interest in anabolic steroids, questionnaires were sent to 1290 family physicians and pediatricians in Texas. Of the 517 respondents, 55% reported being asked about steroids or seeing possible steroid users in their practices during the previous 5 years; 261 physicians (51%) reported 1682 inquiries. High school aged boys were the subject of 60% of all inquiries, 26% of which were made by parents and were exclusively related to sports. Football and athletics in general were the most common reasons for inquiry (62%), but 36% of the adolescents were interested in steroids for psychosocial reasons. Nearly 60% of the inquiries by adolescents and 36% of those by parents were considered to be serious, as opposed to casual. All inquiries regarding adolescents were for boys, and less than 1% were nonwhite. On hundred seventy-seven physicians (34%) reported 802 possible steroid users. Only 17 patients fit the stereotype of a steroid user (ie, competitive bodybuilders or professional and collegiate athletes); football players comprised 12.4% of the total. Those thought to be using steroids for psychosocial reasons equaled almost 10% of the total. All those identified as steroid users were male and only nine were nonwhite. The survey results suggest that interest in and use of anabolic steroids are common, rather than the exclusive purview of competitive athletes. This study is the first to demonstrate parental interest in anabolic steroids.

A program for oriented treatment of essential hypertension.

Treatment of essential hypertension is often a complex task and needs appropriate methodology. A newly developed computer program can help physicians to choose the best pharmacological approach to the treatment of essential hypertension. Based on an oriented clinical history, the program asks the user to give the physiological, pathological and pharmacological antecedents of the patient to be treated. Taking into account these characteristics, 19 antihypertensive drugs are ordered according to their indications and contraindications in the patient. Diet advice based on body weight and the patient's habits are considered as well. The program is designed to explain why decisions are made, so it can be useful in teaching medical students or postgraduates.

Anabolic steroids and growth hormone in the Texas Panhandle.

We conducted a survey of family physicians and general pediatricians in the Texas Panhandle to learn about patient interest in anabolic steroids and growth hormone. Responses were anonymous. Fifty-five percent of those surveyed responded. Of these, 48.5% had received inquiries about anabolic steroids, 29% had seen patients they felt were taking steroids, and 15% had received inquiries concerning growth hormone. All inquirers about steroids and growth hormone and all perceived steroid users were male, and almost all were white. Adolescents (from 13 to 17 years old) accounted for 48% of the inquiries, young adults (18 to 25 years old) 48%, and adults 4%. Twenty percent of the inquiries were made by parents. Adolescents accounted for 31% of the perceived steroid users, young adults 68%, and adults 1%. Weight lifters and body builders comprised 60% of this group, football players 26%, and those taking steroids primarily for psychological reasons 13%. Nearly all inquiries about growth hormone were made by parents, and 44% were made on behalf of children for purposes of augmenting their normal height or for athletic enhancement.