Could nasal septal deformities type 5 and 6 be a predictive factor of the indi- vidual genetic predilection for the onset of an acute coronary syndrome?.

OBJECTIVES: the possible impact of nasal septal deformities (SD) on cardiac pathology has not been well studied, despite growing evidence among data showing that upper air-way obstruction has a negative effect on cardiac function in general and a "deviated nasal septum" being considered one of the most frequent factors responsible for impaired nasal breathing. METHODS: a retrospective, case-control, double-blind study was performed on 249 patients who survived an acute coronary syndrome (ACS) attack. All patients underwent coronary angiography and were divided into coronary angiography positive (123 pts) and coronary angiography negative (126 pts) groups. The quality of nasal breathing was not considered in this study, but morphological aspects of the nasal septum (nasal septal deformities) were observed by anterior native rhinoscopy and endoscopic examination of the nose following the application of superficial anaesthesia. Mladina classification of nasal septal deformities was used. RESULTS: there was a statistically significant difference between coronary angiography negative and positive patients in Mladina type 1 to Mladina type 7 groups (p=0.000, X²=54.605). The incidence of nasal SD types 5 and 6 was higher in the group of ACS patients with the positive coronary angiography, whereas general distribution of the particular types of nasal septal deformities as they appear in the general population was found in the coronary angiography negative group. CONCLUSION: the fact that types 5 and 6 are inherited deformities and not related to trauma against the nose suggests the possible genetic predisposition for the onset of ACS with positive coronary angiography.

Verrucous carcinoma of the foot: a case report.

We present a case of verrucous carcinoma of the foot in a 34-year-old man. This is a rare, locally invasive, well-differentiated, low-grade squamous cell carcinoma, with human papilloma virus as a possible causative agent. It follows a chronic course and mimics a variety of skin lesions, delaying diagnosis by up to 15 years. The definitive diagnosis is made histologically, and treatment by wide local excision is recommended. Our patient underwent wide local excision and partial 5th metatarsal amputation because of invasive disease, local infection, and peripheral vascular disease. There were no postoperative complications. At the 10-year follow-up, there were no signs of tumour recurrence.

Tetrahydrogestrinone is an androgenic steroid that stimulates androgen receptor-mediated, myogenic differentiation in C3H10T1/2 multipotent mesenchymal cells and promotes muscle accretion in orchidectomized male rats.

The discovery of tetrahydrogestrinone (THG) abuse by several elite athletes led the U.S. Congress to declare it a controlled substance, although conclusive evidence of its anabolic/androgenic activity is lacking. We determined whether THG affects myogenic differentiation and androgen receptor (AR)-mediated signaling, whether it binds to AR, and whether it has androgenic and anabolic effects in vivo. Accordingly, we measured the dissociation constant for THG with a fluorescence anisotropy assay using recombinant AR-ligand binding domain. The AR nuclear translocation and myogenic activity of androstenedione were evaluated in mesenchymal, multipotent C3H10T1/2 cells. We performed molecular modeling of the THG:AR interaction. The androgenic/anabolic activity was evaluated in orchidectomized rats. THG bound to AR with an affinity similar to that of dihydrotestosterone. In multipotent C3H10T1/2 cells, THG upregulated AR expression, induced AR nuclear translocation, dose dependently increased the area of myosin heavy chain type II-positive myotubes, and up-regulated myogenic determination and myosin heavy chain type II protein expression. The interaction between AR and the A ring of THG was similar to that between AR and the A ring of dihydrotestosterone, but the C17 and C18 substituents in THG had a unique stabilizing interaction with AR. THG administration prevented the castration-induced atrophy of levator ani, prostate gland, and seminal vesicles and loss of fat-free mass in orchidectomized rats. We conclude that THG is an anabolic steroid that binds to AR, activates AR-mediated signaling, promotes myogenesis in mesenchymal multipotent cells, and has anabolic and androgenic activity in vivo. This mechanism-based approach should be useful for rapid screening of anabolic/androgenic agents.

Peptic ulcer disease in dyspeptic patients with ischemic heart disease: search and treat?

OBJECTIVE: The aim of this study was to determine the prevalence and risk factors for peptic ulcer disease (PUD) in dyspeptic patients with ischemic heart disease (IHD), and to assess whether the healing of PUD before coronary artery bypass grafting (CABG) could reduce the need for urgent postoperative endoscopy. PATIENTS AND METHODS: A series of 894 patients referred to Dubrava University Hospital in Zagreb for elective CABG during the period from May 1998 until April 2001 was prospectively analysed. Dyspepsia was assessed by a questionnaire, PUD by upper gastrointestinal endoscopy, and H. pylori status by histology/Giemsa staining and the rapid urease test. The need for urgent postoperative endoscopy (hematemesis and/or melena, sudden onset of anemia or unexplained epigastric pain) was compared between the prospective study group of 894 patients and a series of 463 patients referred for CABG to Dubrava University Hospital during the period from January 1997 until April 1998. RESULTS: Gastroduodenal dyspepsia predominated in 184 (20.6 %) patients, 142 (77.2 %) of them with Helicobacter (H.) pylori infection and 69 (37.5 %) with verified PUD. Univariate analysis indicated the increased risk of multiple PUD to be related to a previous diagnosis of PUD (OR 3.61, 95 % CI 1.32 - 9.82), H. pylori infection (OR 18.86, 95 % CI 2.31 - 153.98), use of aspirin (OR 5.70; 95 % CI 1.80 - 18.03) and left coronary artery occlusions (3.10, 95 % CI 1.00 - 9.59). Multivariate analysis pointed to H. pylori infection (OR 16.30, 95 % CI 1.57 - 168.53) and left coronary artery occlusions (OR 4.84, 95 % CI 1.05 - 22.30) as independent risk factors for multiple PUD. The OR for urgent postoperative endoscopy due to a major gastrointestinal event was 9.9 (95 % CI 2.2 - 45.1) and the OR for active peptic ulcer with stigmata of recent bleeding was 6.9 (95 % CI 1.4 - 33.1) in the group of patients with IHD who were not submitted to evaluation for dyspepsia prior to elective heart surgery. CONCLUSIONS: In areas with a high prevalence of H. pylori infection, endoscopy and a "search and treat" strategy for IHD patients with dyspepsia before elective cardiac surgery should significantly reduce the need for urgent postoperative endoscopy due to major gastrointestinal events.

Liquid chromatography-tandem mass spectrometry assay for human serum testosterone and trideuterated testosterone.

A liquid chromatography tandem mass spectrometry assay for serum testosterone (T) and trideuterated testosterone (d(3)T) was developed in order to support clinical research studies that determine the pharmacokinetics, production rate, and clearance of testosterone by administration of trideuterated testosterone. After adding 19-nortestosterone as the internal standard (I.S.), sodium acetate buffer, and ether, to a serum aliquot, the mixture was shaken and centrifuged, and the ether was dried. The extract was reconstituted in methanol and 15 microl was injected into a liquid chromatograph equipped with an autosampler and Applied Biosystems-Sciex API 300 triple quadrupole mass spectrometer operated in the positive ion mode. T, d(3)T, and I.S. were monitored with transitions m/z 289 to m/z 97, m/z 292 to m/z 97, and m/z 275 to m/z 109, respectively. The two calibration curves were linear over the entire measurement range of 0-20 ng/ml for T and 0-2.0 ng/ml for d(3)T. The LOQs for T and d(3)T were 0.5 ng/ml and 0.05 ng/ml. The recoveries for T and d(3)T were 91.5 and 96.4%. For T at 1.25 ng/ml and 4.0 ng/ml, the intra-day precision (RSD, %) was 3.9 and 4.3% and intra-day accuracy 0.01 and 4.5%, respectively. The inter-day precision at these levels was 5.3 and 5.4% and inter-day accuracy was 1.9 and 0.3%. For d(3)T at 0.125 ng/ml and 0.4 ng/ml, the intra-day precision (RSD, %) was 2.8 and 8.3% and intra-day accuracy was 1.8 and 5.6%. The inter-day precision at these levels was 10.0 and 7.6% and inter-day accuracy was 5.7 and 3.4%. The concentrations of T in the 38 healthy subjects ranged from 2.5 to 14.0 ng/ml (mean 6.2 ng/ml).

Analysis of over-the-counter dietary supplements.

OBJECTIVE: To determine if steroids containing over-the-counter (OTC) dietary supplements conform to the labeling requirements of the 1994 Dietary Supplement Health and Education Act (DSHEA). DESIGN: 12 brands of OTC supplements containing 8 different steroids were randomly selected for purchase in stores that cater to athletes. There are two androstenediones (4- and 5-androstene-3,17-dione), two androstenediols (4- and 5-androstene-3beta, 17beta-diol), and 4 more are 19-nor cogeners (19-nor-4- and 5-androstene-3,17-dione and 19-nor-4- and 5-androstene-3beta, 17beta-diol). MAIN OUTCOME MEASURES: 12 brands of OTC anabolic-androgenic supplements were analyzed by high-pressure liquid chromatography. RESULTS: We found that 11 of 12 brands tested did not meet the labeling requirements set out in the 1994 Dietary Supplement Health and Education Act. One brand contained 10 mg of testosterone, a controlled steroid, another contained 77% more than the label stated, and 11 of 12 contained less than the amount stated on the label. CONCLUSIONS: These mislabeling problems show that the labels of the dietary steroid supplements studied herein cannot be trusted for content and purity information. In addition, many sport organizations prohibit OTC steroids; thus, athletes who use them are at risk for positive urine test results. In this article we provide the details of the analyses, a summary of the steroids by name and structure, and information on the nature of the positive test results. Athletes and their physicians need this information because of the potential medical consequences and positive urine test results.

Performance characteristics of a carbon isotope ratio method for detecting doping with testosterone based on urine diols: controls and athletes with elevated testosterone/epitestosterone ratios.

BACKGROUND: Carbon isotope ratio methods are used in doping control to determine whether urinary steroids are endogenous or pharmaceutical. METHODS: Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) was used to determine the delta(13)C values for 5 beta-androstane-3 alpha,17 beta-diyl diacetate (5 beta A), 5 alpha-androstane-3 alpha,17 beta-diyl diacetate (5 alpha A), and 5 beta-pregnane-3 alpha,20 alpha-diyl diacetate (5 beta P) in a control group of 73 healthy males and 6 athletes with testosterone/epitestosterone ratios (T/E) >6. RESULTS: The within-assay precision SDs for 5 beta A, 5 alpha A, and 5 beta P were +/- 0.27 per thousand, +/- 0.38 per thousand, and +/- 0.28 per thousand, respectively. The between-assay precision SDs ranged from +/- 0.40 per thousand to +/- 0.52 per thousand. The system suitability and batch acceptance scheme is based on SDs. For the control group, the mean delta(13)C (SD) values were -25.69 per thousand (+/- 0.92 per thousand), -26.35 per thousand (+/- 0.68 per thousand), and -24.26 per thousand (+/- 0.70 per thousand), for 5 beta A, 5 alpha A, and 5 beta P, respectively. 5 beta P was greater than 5 beta A and 5 alpha A (P <0.01), and 5 beta A was greater than 5 alpha A (P <0.01). The means - 3 SD were -28.46 per thousand, -28.39 per thousand, and -26.37 per thousand for 5 beta A, 5 alpha A, and 5 beta P, respectively. The maximum difference between 5 beta P and 5 beta A was 3.2 per thousand, and the maximum 5 beta A/5 beta P was 1.13. Three athletes with chronically elevated T/Es had delta(13)C values consistent with testosterone administration and three did not. CONCLUSIONS: This GC-C-IRMS assay of urine diols has low within- and between-assay SDs; therefore, analysis of one urine sample suffices for doping control. The means, SDs, +/-3 SDs, and ranges of delta(13)C values in a control group are established. In comparison, testosterone users have low 5 beta A and 5 alpha A, large differences between 5 beta A or 5 alpha A and 5 beta P, and high 5 beta A/5 beta P and 5 alpha A/5 beta P ratios.

Dominant right ventricular infarction: is angioplasty the optimal therapeutic approach?

Approximately 30% of all acute inferior myocardial infarctions (AIMI) are accompanied by acute right ventricular infarction (ARVI) as a consequence of proximal right coronary artery (RCA) occlusion. Fifty per cent of all patients with ARVI manifest hypotension, jugular venous distension, and dyspnoea with clear lung fields, which is then considered as dominant acute RVI (ARVI). The in hospital mortality rate of patients with ARVI who are treated traditionally is very high. Thrombolytic therapy is relatively ineffective, while primary angioplasty is a more recent approach yet to be established as optimal treatment for patients with ARVI. Thirty-eight patients with dominant ARVI were admitted to our CCU over a period of 24 months. The patients were retrospectively divided into 3 groups according to treatment: Group I (n = 16): traditional treatment; Group II (n = 12): thrombolytic therapy (streptokinase); Group III (n = 10): angioplasty after urgent coronarography. We tested the difference in the number of deaths in all groups by the Fisher exact test. There was a significant difference in the number of deaths between Group I and Group III (P < 0.05). Mortality reduction was also noted between Group II and Group III, which, however, proved to be statistically insignificant.

Trace contamination of over-the-counter androstenedione and positive urine test results for a nandrolone metabolite.

CONTEXT: Several anabolic steroids are sold over-the-counter (OTC) in the United States, and their production is not regulated by the US Food and Drug Administration. Reports have suggested that use of these supplements can cause positive urine test results for metabolites of the prohibited steroid nandrolone. OBJECTIVES: To assess the content and purity of OTC androstenedione and to determine if androstenedione and 19-norandrostenedione administration causes positive urine test results for 19-norandrosterone, a nandrolone metabolite. DESIGN: Randomized controlled trial of androstenedione, open-label trial of 19-norandrostenedione, and mass spectrometry of androstenedione preparations, conducted between October 1998 and April 2000. SETTING: Outpatient facility of a university hospital. PARTICIPANTS: A total of 41 healthy men aged 20 to 44 years. INTERVENTION: Participants were randomly assigned to receive oral androstenedione, 100 mg/d (n = 13) or 300 mg/d (n = 11) for 7 days, or no androstenedione (n = 13); in addition, 4 patients received 10 microg of 19-norandrostenedione. MAIN OUTCOME MEASURES: Content of OTC androstenedione preparations; level of 19-norandrosterone in urine samples, determined by mass spectrometry, compared among the 3 randomized groups at day 1 and day 7, and among the participants who received 19-norandrostenedione from October 1998 to April 2000. RESULTS: All urine samples from participants treated with androstenedione contained 19-norandrosterone, while no samples from the no-androstenedione group did. Urinary concentrations were averaged for day 1 vs day 7 measurements; mean (SD) 19-norandrosterone concentrations in the 100-mg/d and 300-mg/d groups were 3.8 (2.5) ng/mL and 10.2 (6.9) ng/mL, respectively (P =. 006). The 19-norandrosterone content exceeded the cutoff for reporting positive cases (>2.0 ng/mL) in 20 of 24. The androstenedione preparation used was pure at a sensitivity of 0.1%, but at 0.001% 19-norandrostenedione was found. For the 4 participants to whom 10 microg of 19-norandrostenedione was administered, 19-norandrosterone was found in all urine samples. Of 7 brands of androstenedione analyzed at the 1% level, 1 contained no androstenedione, 1 contained 10 mg of testosterone, and 4 more contained 90% or less of the amount stated on the label. CONCLUSION: Our study suggests that trace contamination of androstenedione with 19-norandrostenedione is sufficient to cause urine test results positive for 19-norandrosterone, the standard marker for nandrolone use. Oral steroid doses as small as 10 microg are absorbed and excreted in urine. Some brands of androstenedione are grossly mislabeled. Careful analysis of androstenedione preparations is recommended in all studies of its biological effects. JAMA. 2000;284:2618-2621.

Influence of erythropoietin treatment on dialyzer reuse.

The effects of recombinant human erythropoietin (r-HuEPO) administration on adequacy of hemodialysis (HD) during single-use versus multiple-reuse of hemophan hollow-fiber dialyzers were assessed in 16 stable end-stage renal disease (ESRD) patients. After 12 months of r-HuEPO treatment and maintenance HD with low-flux single-use dialyzers, in the same group of ESRD patients the effectiveness of automated dialyzer reprocessing using peroxyacetic acid was evaluated. Comparison between r-HuEPO-treated patients dialyzed with single-use devices and those treated with reused dialyzers revealed no significant differences in urea kinetic modelling and nutritional status. However, the duration of HD and heparin dosage were significantly (p < 0.05) increased, and the number of dialyzer uses was properly limited during the reuse program. When dialyzer reprocessing was performed, the r-HuEPO dosage and hemoglobin level remained unchanged if compared with the subgroup treated with single-use dialyzers. It was demonstrated that r-HuEPO treatment did not affect the adequacy of HD, even in case of dialyzer reuse.

Urinary testosterone (T) to epitestosterone (E) ratios by GC/MS. I. Initial comparison of uncorrected T/E in six international laboratories.

Six laboratories in six countries collaborated to investigate the analytical method for estimating the testosterone to epitestosterone ratio (T/E) in urine by gas chromatography/mass spectrometry in the context of detecting the application of T as a doping agent in sport. The protocol specified many but not all details of reagents and instrument conditions. The design included the distribution and analysis of four urines with different T/E values, three replicates per value, and one standard. The ranges of mean T/E values for the four urines estimated by peak area (PA) were 0.32-0.42, 0.72-0.94, 0.91-1.14 and 3.19-5.48. The analyses of variance for these data and for the peak height (PH) data were significant for the laboratory factor (p < 0.0001). In addition there was a significant interaction between the urine factor and the laboratory factor which indicates the complexity of the analysis. T/E calculated using PA was not significantly different from that using PH. For within-laboratory precision all values for PH and PA were < 8.3%, and for between-laboratory precision all values were < 11.7% except for one (20.1%). The data represent a baseline for future experiments designed to elucidate the sources of within-and between-laboratory variance, and to harmonize estimates of T/E.

Improved method of detection of testosterone abuse by gas chromatography/combustion/isotope ratio mass spectrometry analysis of urinary steroids.

The current approach to detection of doping with testosterone is based on measuring the testosterone to epitestosterone ratio (T/E) in urine by gas chromatography/mass spectrometry. The median T/E for healthy males who have not used T is about 1.0. In a single urine, a T/E lower than six leads to a negative report even though it does not exclude T administration. A value greater than six indicates possible T administration or a naturally elevated ratio. It has been shown previously that the carbon isotope ratio of urinary T changes after T administration. In this study a potential confirmation method for T abuse was optimized. Gas chromatography/combustion/carbon isotope ratio mass spectrometry (GC/C/IRMS) was used to analyze two T precursors (cholesterol and 5-androsten-3 beta, 17 beta-diol) and two T metabolites (5 alpha- and 5 beta-androstane-3 alpha, 17 beta-diol) in addition to T itself in each of 25 blind urines collected from eight healthy men before, during or after T administration. The carbon isotope ratios of T and the metabolites were lower after T administration. The relationships among the variables were studied using multivariate analysis and beginning with principal components analysis; cluster analysis revealed that the data are composed of two clusters, and classified the samples obtained after T administration in one cluster and the remainder in the other; discriminant analysis correctly identified T users. The measurement of carbon isotope ratios of urinary androgens is comparable to the T/E > 6 test and continues to show promise for resolving cases where doping with T is suspected.