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At least 145 records · Page 8Linked to original sources
PubMed2003

Blunted increase in plasma adenosine levels following dipyridamole stress in dilated cardiomyopathy patients.

BACKGROUND: Heart failure is characterized by chronically increased adenosine levels, which are thought to express a protective anti-heart failure activation of the adenosinergic system. The aim of the study was to assess whether the activation of adenosinergic system in idiopathic dilated cardiomyopathy (IDC) can be mirrored by a blunted increase in plasma adenosine concentration following dipyridamole stress, which accumulates endogenous adenosine. METHODS: Two groups were studied: IDC patients (n = 19, seven women, mean age 60 +/- 12 years) with angiographically confirmed normal coronary arteries and left ventricular ejection fraction <35%; and normal controls (n = 15, six women, mean age 68 +/- 5 years). Plasma adenosine was assessed by high-performance liquid chromatography methods in blood samples from peripheral vein at baseline and 12 min after dipyridamole infusion (0.84 mg kg-1 in 10 min). RESULTS: At baseline, IDC patients showed higher plasma adenosine levels than controls (276 +/- 27 nM L-1 vs. 208 +/- 48 nM L-1, P < 0.001). Following dipyridamole, IDC patients showed lower plasma adenosine levels than controls (322 +/- 56 nM L-1 vs. 732 +/- 250 nM L-1, P < 0.001). The dipyridamole-induced percentage increase in plasma adenosine over baseline was 17% in IDC and 251% in controls (P < 0.001). By individual patient analysis, 18 IDC patients exceeded (over the upper limit) the 95% confidence limits for normal plasma adenosine levels at baseline, and all 19 exceeded (below the lower limit) the 95% confidence limits for postdipyridamole plasma adenosine levels found in normal subjects. CONCLUSION: Patients with IDC have abnormally high baseline adenosine levels and--even more strikingly--blunted plasma adenosine increase following dipyridamole infusion. This is consistent with a chronic activation of the adenosinergic system present in IDC, which can be measured noninvasively in the clinical theatre.

Adenosine↗
PubMed1996

Comparison of multivariate predictive power of major risk factors for coronary heart diseases in different countries: results from eight nations of the Seven Countries Study, 25-year follow-up.

BACKGROUND: It was hypothesized that among eight national groups of men aged 40-59 years enrolled in the Seven Countries Study, the multivariate coefficients of major risk factors predicting coronary heart disease mortality over 25 years would be relatively similar. MATERIALS AND METHODS: Sixteen cohorts were located in eight nations and pooled, comprising one cohort in the USA, two in Finland, one in the Netherlands, three in Italy, two in Croatia (former Yugoslavia), three in Serbia (Yugoslavia), two in Greece and two in Japan, for a total of over 12000 subjects at entry. Coronary heart disease (CHD) mortality was defined as fatal myocardial infarction or sudden coronary death, and proportional hazard models were solved, for each country, with age, serum cholesterol level, systolic blood pressure and cigarette consumption as covariates. RESULTS: The relationships between risk factors and CHD mortality were statistically significant for all risk factors and for all countries, except for age in Croatia and Japan, cholesterol in Croatia and Japan, systolic blood pressure in Serbia and Greece, and cigarette-smoking in the Netherlands, Croatia, Serbia and Greece. When comparing all pairs of coefficients (28 comparisons for each factor) significant differences were found on four occasions for age, on six occasions for cholesterol, on no occasion for blood pressure and on four occasions for cigarette-smoking. Other tests suggested a substantial homogeneity among multivariate coefficients. Estimates for pooled coefficients were: age, in years, 0.0570 (95% confidence limits 0.0465 and 0.0673); relative risk for 5 years 1.33 (95% confidence limits 1.26 and 1.40); serum cholesterol level in mg/dl, 0.0057 (95% confidence limits 0.0045 and 0.0069); relative risk for 40 mg/dl 1.31 (95% confidence limits 1.20 and 1.31); systolic blood pressure in mmHg, 0.0160, (95% confidence limits 0.0134 and 0.0185), relative risk for 20 mmHg 1.38 (95% confidence limits 1.31 and 1.45); cigarettes per day, 0.0220 (95% confidence limits 0.0170 and 0.0272); relative risk for 10 cigarettes per day 1.25 (95% confidence limits 1.18 and 1.31). CONCLUSIONS: Great similarities were found in the multivariate coefficients of major coronary risk factors to CHD risk derived from population samples varying in CHD frequency.

Adult↗
PubMed1987

Time trends and occupational differences in cancer of the testis in New Zealand.

The findings are reported from a New Zealand Cancer Registry-based case-control study involving 427 male patients with testicular cancer registered during the period 1979-1983 and aged 20 years or more at time of registration. Controls were also males chosen from the Cancer Registry with two controls per case, matched on age and year of registration. It was found that, as in other countries, persons in the upper social class groupings were at increased risk of testicular cancer. Persons in professional occupations were also at increased risk, but the odds ratio of 1.09 was much smaller than found in other studies. The previously reported excess risks for farmers, food and beverage workers, forestry workers, and pulp and paper workers were not supported by the New Zealand data. On the other hand, the previously reported excess risk for sales and service workers including members of the armed forces was supported, to some extent, by the New Zealand data with odds ratios of 1.38 (95% confidence limits 0.98-1.93) and 2.15 (95% confidence limits 0.80-5.79), respectively. Other groups with elevated risk include: physicians (odds ratio = 6.50, 95% confidence limits 1.29-32.6); production supervisors (odds ratio = 2.85,95% confidence limits 1.00-8.13); and motor vehicle mechanics (odds ratio = 2.02, 95% confidence limits 0.93-4.42). However, the New Zealand data generally does not suggest that occupational factors (or lifestyle factors associated with occupation) are of major direct importance in the etiology of testicular cancer. The incidence of testicular cancer has a bimodal age distribution in New Zealand and has risen markedly during the period 1948-1979. The New Zealand data differed from patterns observed in other countries in that the relative increase was approximately uniform across age groups rather than being stronger in the younger age groups.

Age Factors↗
PubMed2002

Intermediate follow-up of a composite stentless porcine valved conduit of bovine pericardium in the pulmonary circulation.

BACKGROUND: In the pediatric population, glutaraldehyde-preserved bovine pericardium conduit containing a stentless porcine valve has been proposed as an alternative to homografts for right ventricular outflow tract reconstruction. METHODS: Between June 1996 and March 2000, a total of 55 patients, 20 with truncus arteriosus, 21 with pulmonary atresia with ventricular septal defect, and 14 with miscellaneous defects, received this conduit. Median age at implantation was 3.4 months (range, 3 days to 19 years), and 27 patients (50%) were less than 3 months old. Clinical outcome, echocardiographic data, and pathologic analysis were recorded. End points for conduit failure were conduit replacement or dilation. A mean follow-up of 27 months (range, 2 to 46 months) was available for 47 survivors. RESULTS: Procedure for conduit obstruction was required in 13 patients. The most common procedure was operation, and all but 3 patients had an unsuccessful balloon angioplasty before reoperation. Actuarial freedom from conduit dilation or reoperation was 93.6% (95% confidence limits, 82% to 99%), 81.9% (95% confidence limits, 64% to 91%), 77.8% (95% confidence limits, 39% to 78%), and 64.3% (95% confidence limits, 26% to 73%) at 1, 2, 3, and 4 postoperative years, respectively. Univariate analysis identified small conduit size as a risk factor for conduit obstruction. CONCLUSIONS: Although this new conduit was not free from progressive obstruction, our clinical results (easy to work and good valvular function) and the availability in small sizes encouraged us to use it as an alternative to small-size homografts when those were not available.

Adolescent↗
PubMedDate not supplied

A bioequivalence study of levothyroxine tablets versus an oral levothyroxine solution in healthy volunteers.

Probably for genetic reasons a substantial part of the Greek population requires Levothyroxine treatment. Since commercially available Levothyroxine was first marketed, the manufacture and storage of the drug in tablet form has been complicated and difficult; and as cases of therapeutic failure have frequently been reported following treatment with this medicinal agent, quality control is an essential factor. Due to the unreliability of Levothyroxine-based commercial products, in the present study we decided to follow the Food and Drug Administration (FDA) guidelines*, and use a Levothyroxine solution as reference product. The bioavailability of the Levothyroxine sodium tablet formulation THYROHORMONE/Ni-The Ltd (0.2 mg/tab) and that of a reference oral solution (0.3 mg/100 ml) under fasting conditions were compared in an open, randomized, single-dose two-way crossover study. Twenty four healthy Caucasian volunteers (M/F=15/9, mean age=32.9+/-7.4yr) participated in the study. Bioavailability was assessed by pharmacokinetic parameters such as the area under plasma concentration-time curve from time zero up to the measurable last time point (AUC(last)) and the maximum plasma concentration (Cmax). Heparinized venous blood samples were collected pre-dose and up to a 48-hour period post-dose. Levothyroxine sodium in plasma samples was assayed by a validated electrochemiluninescent immunoassay technique. Statistical analysis showed that the post-dose thyrotropin-stimulating hormone (TSH) levels decreased significantly (p<0.05). Regarding Levothyroxine (T4), the point estimate of the test formulation to the reference formulation ratios (T/R) for AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.94) and 0.93 with 90% confidence limits (0.91, 0.94), respectively. Regarding triiodo-L-thyronine (T3), the point estimate for the T/R ratios of AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.95) and 0.94 with 90% confidence limits (0.92, 0.95), respectively. The 90% confidence limits for the pharmacokinetic parameters AUC(last) and Cmax lie within the acceptance limits for bioequivalence (0.80, 1.25), for both T3 and T4.

Administration, Oral↗
PubMed1992

Transposition of the great arteries, ventricular septal defect, and pulmonary outflow tract obstruction. Rastelli or Lecompte procedure?

During a 10-year period (1980 to 1990), 62 patients underwent complete repair for transposition of the great arteries, ventricular septal defect, and pulmonary outflow tract obstruction. Twenty-two patients (35%) (mean age 8.1 +/- 7.2 years) underwent the Rastelli operation: The ventricular septal defect was enlarged anteriorly in eight patients, and right ventricular-pulmonary artery continuity was established with an extracardiac valved (9/22) or nonvalved (13/22) conduit. Forty patients (65%) (mean age 3.3 +/- 3.2 years) underwent the Lecompte modifications: The conal septum was extensively excised when present (30/40), anterior translocation of the pulmonary bifurcation was performed in 32 patients, and right ventricular-pulmonary artery continuity was established by direct anastomosis without a prosthetic conduit. There were seven early deaths (11%; 70% confidence limits, 7% to 17%): two after the Rastelli procedure (9%; 70% confidence limits, 3% to 20%) and five after the Lecompte operation (12.5%; 70% confidence limits, 7% to 20%). Four patients were lost to follow-up, yielding a 93% complete follow-up (mean follow-up 55 months). There were two late deaths (one in each group). Actuarial probability of survival (+/- standard error) at 5 years was 83% +/- 9% after the Rastelli operation and 84% +/- 6% after the Lecompte procedure. All long-term survivors (except one in the Rastelli group) were in functional class I. Five patients in the Rastelli group underwent late reoperation for obstruction of the extracardiac conduit (28%; 70% confidence limits, 16% to 42%). Three late reoperations (10%; 70% confidence limits, 4% to 19%) were required after the Lecompte operation (one for residual ventricular septal defect and two for residual pulmonary outflow tract obstruction). At most recent examination, residual pulmonary outflow tract obstruction was present in seven patients of the Rastelli group (39%; 70% confidence limits, 26% to 53%) and in six patients of the Lecompte group (19%; 70% confidence limits, 12% to 29%). The combined likelihood of reoperation for pulmonary outflow tract obstruction and residual pulmonary outflow tract obstruction was significantly higher in the Rastelli group (67% versus 26%; p = 0.005). Both procedures provide satisfactory early and late results. The Lecompte operation allows complete repair in infancy, is feasible in patients with anatomic contraindications to the Rastelli operation, and may reduce the need for reoperation and the prevalence of residual pulmonary outflow tract obstruction.

Abnormalities, Multiple↗
PubMed1989

The nasopharyngeal bacterial flora in the sudden infant death syndrome.

The nasopharyngeal bacterial flora in babies who had died of the sudden infant death syndrome (SIDS) (n = 46) and in healthy infants aged 2 weeks to 6 months (n = 46) is described. Of those who had died, 41.3% carried Staphylococcus aureus (95% confidence limits: 27.3-55.3%) compared with 28.3% of healthy infants (95% confidence limits: 15.3-41.3%). The isolation rate of streptococci was 78.3% in cases (95% confidence limits: 66.4-90.2%) and 32.6% in healthy infants (95% confidence limits: 19.1-46.1%) (significant difference P less than 0.0001). Enterobacteria were isolated from 45.6% of cases (95% confidence limits: 31.2-60%) but only 2.2% of healthy infants (95% confidence limits 0-6.4%) (significant difference, P less than 0.0001). These results indicate a disordered nasopharyngeal flora in SIDS. They also provide baseline data for investigating the hypothesis that common bacterial toxins are involved in the pathogenesis of SIDS.

Bacteria↗
PubMed1988

Angiographic studies of internal mammary artery grafts 11 years after coronary artery bypass grafting.

Of 99 consecutive patients with 101 internal mammary artery grafts, 91 of 97 hospital survivors (94%) underwent angiography 2 weeks after operation, 84 of 96 survivors (88%) after 1 year, 66 of 88 survivors (75%) after 5 years, and 37 of 69 survivors (54%) after 11 years (range 10 to 13 years). Thirty-five of the 37 patients who consented to a fourth postoperative angiographic study (95%, confidence limits 86% to 100%) still reported relieved angina 11 years after the operation, and seven patients (19%, confidence limits 5% to 33%) were completely free of symptoms. Angiographic findings in 30 patients with symptoms of angina were progression of the coronary artery disease in 22, (73%, confidence limits 56% to 91%), occluded or stenosed grafts in nine (30%, confidence limits 12% to 48%), and nonbypassed obstructions in six patients (20%, confidence limits 4% to 36%). The cumulative 11-year patency rate was 88%, confidence limits 81% to 95%, for internal mammary artery grafts and 61%, confidence limits 45% to 76% for saphenous vein grafts. Six of 18 saphenous vein grafts (33%, confidence limits 19% to 58%) occluded in the interval between 5 and 11 years after operation, and gross wall irregularities were observed in six of the 12 patent saphenous vein grafts. Unligated side branches and stenosis of the internal mammary artery did not prevent long-term graft patency. Internal mammary artery graft failures were related to technical errors during the operation and occurred when the internal mammary artery was used to bypass a low-grade coronary artery stenosis. In one patient, regression of a coronary artery stenosis was associated with a marked decrease in luminal size of the internal mammary artery graft before the 5-year follow-up. This single internal mammary artery graft became occluded in the interval between 5 and 11 years after the operation. Eleven of 36 internal mammary artery grafts (31%, confidence limits 14% to 47%) increased 15% to 40% in luminal diameter as a result of increased myocardial blood demand before the 11-year follow-up.

Angiography↗
PubMed1989

Linkage relationships of gene loci in the Medaka, Oryzias latipes (Pisces: Oryziatidae), determined by backcrosses and gynogenesis.

Linkage relationships of 11 enzyme loci and 2 visible mutant loci were investigated in the Medaka, Oryzias latipes, using backcrosses and gynogenesis. Results of four crosses for three loci were not in agreement with the Mendelian expectation of a 1 homozygote:1 heterozygote segregation ratio. Some locus pairs showed a significant excess of parental types at the 5% confidence limit. At the 1% confidence limit, however, results of all locus pairs analyzed showed nonsignificance. The results of sex-linked locus tests showed that no loci were sex linked at the 1% confidence limit. Under complete interference conditions, gene-centromere distances (cM) were as follows: Me, 2.6; Adh, 10; Sod, 17; Sdh, 18; Pgm, 31; Ck-A, 31; Gpdh, 32; Pgd, 45; Amy, 47; and Ldh-A, 50. High heterozygous fractions observed for Pgd, Amy, and Ldh-A suggest that exactly one crossover happened between these genes and their centromeres and that strong interference exists in chromosomes carrying these loci.

Animals↗
PubMed1980

The recurrence risk for neural tube defects in the United States: a collaborative study.

To determine the recurrence risk for patients with one prior pregnancy affected with neural tube defects (NTD), the authors have pooled data from eight testing centers. In 831 pregnancies studied because one sib was affected with an NTD, the recurrence rate was 3.0%, with 95% confidence limits of 2.0-4.3%, and 99% confidence limits of 1.8-4.8%. The recurrent lesion, whether spina bifida or anencephaly, tended to be concordant with the first to a significant degree. Only 12.2% of recurrent NTD were different from the first, with 95% confidence limits of 4.1-26.2%, and 99% confidence limits of 1.7-30.9%. Both an accurate recurrence risk and the information that a recurrent NTD lesions tends to be concordant with that in the first affected child are useful in the genetic counseling of patients in the United States and in the selection of appropriate prenatal diagnostic studies.

Female↗
PubMed1999

The epidemiology of cataract in Australia.

PURPOSE: To describe the prevalence and risk factors for cataract in an Australian population aged 40 years and older. METHODS: Participants were recruited by a household census and stratified, random cluster sampling to represent residents of Victoria, Australia, aged 40 years and older. The following information was collected: initial visual acuity and best-corrected visual acuity, demographic details, health history, dietary intake of antioxidants, lifetime ocular ultraviolet B exposure, and clinical eye examination, including lens photography. Cortical opacities were measured in sixteenths. Cortical cataract was defined as opacity greater than or equal to 4/16 of pupil circumference. Nuclear opacities were graded according to the Wilmer cataract grading scheme, and cataract was defined as greater than or equal to nuclear standard 2.0 of four standards. The height and width of any posterior subcapsular opacity was measured and recorded. Posterior subcapsular cataract was defined as posterior subcapsular opacity greater than or equal to 1 mm2. The worse eye was selected for analysis. Backward stepwise logistic regression was used to quantify independent risk factors for cataract. RESULTS: A total of 3,271 (83% of eligible) of the urban residents, 403 (90% of eligible) nursing home residents, and 1,473 (92% of eligible) rural residents participated. The urban residents ranged in age from 40 to 98 years (mean, 59 years), and 1,511 (46%) were men. The nursing home residents ranged in age from 46 to 101 years (mean, 82 years), and 85 (21%) were men. The rural residents ranged in age from 40 to 103 years (mean, 60 years), and 701 (47.5%) were men. The overall weighted rate of cortical cataract was 11.3% (95% confidence limits, 9.68%, 13.0%) excluding cataract surgery and 12.1% (95% confidence limits, 10.5%, 13.8%) including cataract surgery. The risk factors for cortical cataract that remained in the multivariate logistic regression model were age, female gender, diabetes duration greater than 5 years, gout duration greater than 10 years, arthritis diagnosis, myopia, use of oral beta-blockers, and increased average annual ocular ultraviolet B exposure. Overall, 12.6% (95% confidence limits, 9.61%, 15.7%) of Victorians aged 40 years and older had nuclear cataract including previous cataract surgery, and 11.6% (95% confidence limits, 8.61%, 14.7%) had nuclear cataract excluding previous cataract surgery. In the urban and rural cohorts, age, female gender, rural residence, brown irides, diabetes diagnosed 5 or more years earlier, myopia, age-related maculopathy, having smoked for greater than 30 years, and an interaction between ocular ultraviolet B exposure and vitamin E were all risk factors for nuclear cataract. The rate of posterior subcapsular cataract excluding previous cataract surgery was 4.08% (95% confidence limits, 3.01%, 5.14%), whereas the overall rate of posterior subcapsular cataract including previous cataract surgery was 4.93% (95% confidence limits, 3.68%, 6.17%) . The independent risk factors for posterior subcapsular cataract in the urban and rural cohorts that remained were age in years, rural location, use of thiazide diuretics, vitamin E intake, and myopia. CONCLUSIONS: The expected increase in the prevalence of cataract with the aging of the population highlights the need to plan appropriate medical services and public health interventions for primary and secondary prevention. Many of the identified risk factors for cataract in the population have the potential for being modified through public health interventions.

Adult↗
PubMed1999

Monte Carlo mixture model of lifetime cancer incidence risk from radiation exposure on shuttle and international space station.

Estimating uncertainty in lifetime cancer risk for human exposure to space radiation is a unique challenge. Conventional risk assessment with low-linear-energy-transfer (LET)-based risk from Japanese atomic bomb survivor studies may be inappropriate for relativistic protons and nuclei in space due to track structure effects. This paper develops a Monte Carlo mixture model (MCMM) for transferring additive, National Institutes of Health multiplicative, and multiplicative excess cancer incidence risks based on Japanese atomic bomb survivor data to determine excess incidence risk for various US astronaut exposure profiles. The MCMM serves as an anchor point for future risk projection methods involving biophysical models of DNA damage from space radiation. Lifetime incidence risks of radiation-induced cancer for the MCMM based on low-LET Japanese data for nonleukemia (all cancers except leukemia) were 2.77 (90% confidence limit, 0.75-11.34) for males exposed to 1 Sv at age 45 and 2.20 (90% confidence limit, 0.59-10.12) for males exposed at age 55. For females, mixture model risks for nonleukemia exposed separately to 1 Sv at ages of 45 and 55 were 2.98 (90% confidence limit, 0.90-11.70) and 2.44 (90% confidence limit, 0.70-10.30), respectively. Risks for high-LET 200 MeV protons (LET=0.45 keV/micrometer), 1 MeV alpha-particles (LET=100 keV/micrometer), and 600 MeV iron particles (LET=180 keV/micrometer) were scored on a per particle basis by determining the particle fluence required for an average of one particle per cell nucleus of area 100 micrometer(2). Lifetime risk per proton was 2.68x10(-2)% (90% confidence limit, 0.79x10(-3)%-0. 514x10(-2)%). For alpha-particles, lifetime risk was 14.2% (90% confidence limit, 2.5%-31.2%). Conversely, lifetime risk per iron particle was 23.7% (90% confidence limit, 4.5%-53.0%). Uncertainty in the DDREF for high-LET particles may be less than that for low-LET radiation because typically there is very little dose-rate dependence. Probability density functions for high-LET radiation quality and dose-rate may be preferable to conventional risk assessment approaches. Nuclear reactions and track structure effects in tissue may not be properly estimated by existing data using in vitro models for estimating RBEs. The method used here is being extended to estimate uncertainty in spacecraft shielding effectiveness in various space radiation environments.

Adult↗
PubMed2006

Evaluation of statistical methods for left-censored environmental data with nonuniform detection limits.

Monte Carlo simulations were used to evaluate statistical methods for estimating 95% upper confidence limits of mean constituent concentrations for left-censored data with nonuniform detection limits. Two primary scenarios were evaluated: data sets with 15 to 50% nondetected samples and data sets with 51 to 80% nondetected samples. Sample size and the percentage of nondetected samples were allowed to vary randomly to generate a variety of left-censored data sets. All statistical methods were evaluated for efficacy by comparing the 95% upper confidence limits for the left-censored data with the 95% upper confidence limits for the noncensored data and by determining percent coverage of the true mean (micro). For data sets with 15 to 50% nondetected samples, the trimmed mean, Winsorization, Aitchison's, and log-probit regression methods were evaluated. The log-probit regression was the only method that yielded sufficient coverage (99-100%) of micro, as well as a high correlation coefficient (r2 = 0.99) and small average percent residuals (-0.1%) between upper confidence limits for censored versus noncensored data sets. For data sets with 51 to 80% nondetected samples, a bounding method was effective (r2 = 0.96 - 0.99, average residual = -5% to -7%, 95-98% coverage of micro), except when applied to distributions with low coefficients of variation (standard deviation/micro < 0.5). Thus, the following recommendations are supported by this research: data sets with 15 to 50% nondetected samples--log-probit regression method and use of Chebyshev theorem to estimate 95% upper confidence limits; data sets with 51 to 80% nondetected samples-bounding method and use of Chebyshev theorem to estimate 95% upper confidence limits.

Computer Simulation↗
PubMed2004

[Effect of 4-ethylamino-2-butynyl(2-cyclohexyl-2-phenyl) glycolate, metabolite of oxybutynin, on intra-artery administered acetylcholine-induced urinary bladder contraction in anesthetized dogs].

Oxybutynin has been used for neurogenic bladder disorders in clinic and known to have anti-cholinergic and spasmolytic properties. Metabolite of oxybutynin, 4-ethylamino-2-butynyl(2-cyclohexyl-2-phenyl) glycolate (N-desethyloxybutynin: DEOB) has been known to have similar anti-cholinergic and spasmolytic properties. However, the effect of DEOB on the urinary bladder has not been clarified in situ. Therefore, in the present study, we studied the effect of DEOB on acetylcholine-induced urinary bladder contraction in comparison with oxybutynin in anesthetized dogs. Intravenously administered DEOB dose-dependently inhibited acetylcholine-induced contractions. Oxybutynin also showed similar efficacy. From the Schild plot, it was found that the slope of DEOB and oxybutynin were 0.78 (95% confidence limit: 0.45-1.11) and 1.49 (95% confidence limit: 0.91-2.08), respectively. The dose of DEOB or oxybutynin needed to shift the concentration-dependent curve of acetylcholine rightward to a two times higher dose was calculated. The doses of DEOB and oxybutynin were 6.4 micro g/kg (95% confidence limit: 1.7-12.8 micro g/kg) and 13.9 micro g/kg (95% confidence limit: 6.3-24.5 micro g/kg), respectively. From the above results, it was found that DEOB has the same anti-cholinergic property as oxybutynin and that its activity was almost equipotent to that of oxybutynin. Therefore, DEOB was suggested to play an important role during oxybutynin therapy for neurogenic bladder disorder.

Acetylcholine↗
PubMed1992

In vitro activity of teicoplanin and vancomycin against gram-positive bacteria from human clinical and veterinary sources.

The minimum inhibitory concentration (MIC) of teicoplanin and vancomycin was determined by the agar dilution method for 186 Gram-positive bacteria from human clinical and veterinary sources. Teicoplanin MIC values were less than or equal to 4 micrograms/ml for 94% of staphylococci (group A, n = 52) and less than or equal to 2 micrograms/ml for all streptococci, enterococci, aerococci and pediococci (group B, n = 75). Seventy-eight percent of Gram-positive rods, Rhodococcus and Leuconostoc spp. (group C, n = 59) were inhibited by 4 micrograms/ml. Teicoplanin resistance (MIC greater than or equal to 16 micrograms/ml) was demonstrated for all Nocardia strains and for some strains of Lactobacillus, E. rhusiopathiae, Leuconostoc, and S. haemolyticus. Cross-resistance between teicoplanin and vancomycin was observed for all Nocardia strains and for some strains of Lactobacillus, E. rhusiopathiae, and Leuconostoc. Three methicillin-resistant S. haemolyticus strains were either resistant or intermediately susceptible to teicoplanin and susceptible to vancomycin. Eight strains (motile enterococci four, E. rhusiopathiae three and Leuconostoc sp. one) were susceptible to teicoplanin and resistant to vancomycin. Teicoplanin disc diffusion on Danish Blood Agar with NeoSensitabs (Rosco), PDM AB Biodisc and locally prepared discs revealed a wide range of zone diameters in groups B and C. The relation between MIC values and zone diameters for teicoplanin was analysed by the error-rate bounded method. Zone size interpretive criteria as suggested by the manufacturers (greater than or equal to 15 mm) produced 2.7% (95% confidence limits 0.9-6.2%) and 1.6% (95% confidence limits 0.3-4.6%) very major errors for NeoSensitabs and PDM-disc, respectively. Using a zone size breakpoint for susceptibility of greater than or equal to 25 mm for NeoSensitabs and greater than or equal to 20 mm for PDM-disc, the proportions of very major errors were 0.5% (95% confidence limits 0.0-3.0%) at the expense of 5.9% (95% confidence limits 3.0-10.3%) indeterminate strains that belonged to E. rhusiopathiae, Leuconostoc, Lactobacillus and S. haemolyticus. However, using these zone size breakpoints five major errors (beta-haemolytic streptococci, group B three, S. aureus one, Leuconostoc sp. one) were observed for NeoSensitabs and two major errors (beta-haemolytic streptococcus, group B one, Leuconostoc sp. one) were observed for PDM-disc. Susceptibility testing against teicoplanin among these taxa should therefore include a determination of MIC.

Animals↗
PubMed2000

The analgesic efficacy of topical capsaicin is enhanced by glyceryl trinitrate in painful osteoarthritis: a randomized, double blind, placebo controlled study.

The aim of this study was to assess if the pain of osteoarthritis is reduced by topical capsaicin and to determine whether addition of glyceryl trinitrate has an effect on analgesic efficacy and tolerability of capsaicin. A randomized, double blind, placebo controlled study was carried out on 200 adult patients attending a Pain Clinic with osteoarthritis pain. Patients applied one of four creams topically over the affected joint over a 6 week period. Creams contained either placebo (vehicle), 0.025% capsaicin, 1.33% glyceryl trinitrate or 0.025% capsaicin + 1.33% glyceryl trinitrate. Analgesic efficacy, tolerability of cream and analgesic consumption were assessed. One hundred and sixty-seven of 200 patients completed the study. Baseline visual analogue scores (0-10 scale) for pain were 6.40. There was a significant reduction in pain scores in the glyceryl trinitrate group (mean decrease 0.59, p< 0.05, 95% confidence limits 0.04-1.14), 0.025% capsaicin group (mean decrease 0.5, p< 0.05, 95% confidence limits 0.05-1.05) and the glyceryl trinitrate capsaicin group (mean decrease 1.1, p<0.05, 95% confidence limits 0.22-1.98). Baseline discomfort of application scores were similar for all but the capsaicin groups (they were significantly higher (by 2.1 units, p< 0.001)). The odds ratio in favour of continuing treatment was 2.1 (95% confidence limits 1.0-4.4) for glyceryl trinitrate and 2.4 (95% confidence limits 1.2-5.1) for capsaicin and 5.0 (95% confidence limits 3.8-6.4) for capsaicin GTN combination. The study showed that topical capsaicin and glyceryl trinitrate have an analgesic effect in painful osteoarthritis. When used together this effect is increased with the combination being more tolerable than capsaicin alone. Analgesic consumption is decreased by capsaicin, glyceryl trinitrate and to a greater extent by both combined.

Administration, Topical↗
PubMed1993

Preliminary results with neoadjuvant therapy and resection for esophageal carcinoma.

Between December 1988 and August 1992, 68 patients with adenocarcinoma (n = 39) and squamous carcinoma (n = 29) of the esophagus were entered prospectively in a treatment protocol to receive two cycles of cisplatin, 5-fluorouracil, etoposide, leucovorin, and 3,000 cGy of radiation to the involved esophagus and adjacent mediastinum, followed by resection. There were four deaths during chemotherapy, and 7 patients had a decline in condition or were denied operation. Fifty-six patients have come to operation, and 1 awaits resection. Twenty-two patients had transhiatal esophagectomy and 29 patients had esophagogastrostomy with a combined abdominal and right thoracic approach. Five patients did not undergo resection at operation. There was one hospital death (2%). A complete response to preoperative therapy was seen in 12 patients (21%): 5 of 20 with squamous cancer (25%) and 7 of 36 with adenocarcinoma (19%). Average follow-up is 19 months. Median survival in these patients after entrance in the protocol is 24 months. Actuarial survival at 12, 18, and 24 months is 72% (confidence limits, 66% and 78%), 53% (confidence limits, 46% and 60%), and 51% (confidence limits, 44% and 58%). Significantly better survival was associated with adenocarcinoma (p = 0.041). There is no survival advantage based on complete response to preoperative therapy. This neoadjuvant regimen is effective in patients with squamous carcinoma and adenocarcinoma. These preliminary results demonstrate an improved median and actuarial survival compared with historical controls in 137 patients operated on between 1966 and 1985 at our institution.

Adenocarcinoma↗
PubMed1995

Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population.

The occurrence of multiple copies of the CYP2D6 gene was investigated 217 white healthy Spaniards by the combined use of Xba I and Eco RI restriction fragment length polymorphism (RFLP) analyses. About 3.5% of the alleles yielded an 12.1 kb Eco RI-RFLP product in combination with the 42 kb Xba I-RFLP product, which is indicative of multiple CYP2D6. The prevalence of subjects carrying multiple CYP2D6 was 7%. The 12.1 kb Eco RI-RFLP product was highly associated (60%) with the presence of the genotype 29wt/42wt, as characterized by mutation-specific polymerase chain reaction and Xba I-RFLP analyses. Six subjects who had multiple CYP2D6 had other genotypes, namely, 44wt/42wt (four subjects), 29C/42wt (one subject), and one subject had a 12.1 kb product plus the CYP2D6C mutation associated with the 44 kb/42 kb genotype. All subjects identified as carrying multiple CYP2D6 had only two CYP2D6 copies in the same chromosome and were classified as carriers of the (CYP2D6L)2 allelic variant. Phenotyping with debrisoquin indicated an increase in the oxidative capacity as a function of the number of functional CYP2D6 genes. The metabolic ratio and the 95% confidence limits were as follows: subjects lacking functional genes, 48.8 (95% confidence limits, 14.4 to 79.3); subjects with one functional gene, 2.14 (95% confidence limits, 0.61 to 3.67); subjects with two functional genes, 1.5 (95% confidence limits, 0.88 to 2.14); and subjects with three functional genes, 0.33 (95% confidence limits, 0.22 to 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)

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