The accuracy of BI-RADS classification of breast ultrasound as a first-line imaging method.

PURPOSE: The aim was to evaluate the accuracy of BI-RADS categories 3 - 5 in breast ultrasound (US) as the first-line imaging method. MATERIALS AND METHODS: 5077 examinations of a consecutive, unselected and mixed collective of symptomatic and asymptomatic patients were performed. Of these examinations, 835 cases of BIRADS 3 - 5 could be analyzed. RESULTS: The PPV with respect to a malignant lesion for BI-RADS 3, 4, 5 was 0.03, 0.48, and 0.97, respectively. When BI-RADS 4 and 5 cases are considered to be suspicious, the ratio of benign to malignant findings corresponds to 1:1.8. Analyzing BIRADS 3 - 5 lesions, the sensitivity, specificity and accuracy are 0.92, 0.85, and 0.87, respectively. CONCLUSION: The data support the feasibility of US for discriminating malignant from benign findings corresponding to the ACR BI-RADS classification without excessively increasing the number of unnecessary biopsies.

[The suitability of high-resolution ultrasound for the detection of DCIS]. / Die Eignung der hochfrequenten Sonografie zur Diagnostik des DCIS.

PURPOSE: Presentation of the suitability of breast ultrasound for detecting DCIS of the breast. MATERIALS AND METHODS: Review of literature on the topic and description of the sonographic features of DCIS illustrated by cases. RESULTS: Breast ultrasound is currently capable of detecting DCIS with a comparable success rate to that of mammography. The advantages of sonography become obvious in cases of DCIS without microcalcifications and DCIS in dense or very dense breasts. The assessment of the sonographic architecture of the whole lobe, not just circumscribed lesions, is becoming increasingly important. CONCLUSION: Breast ultrasound represents an important tool for detecting DCIS in addition to mammography.

[Re-evaluating the role of breast ultrasound in current diagnostics of malignant breast lesions]. / Neubewertung der Mammasonographie in der gegenwärtigen Mammakarzinomdiagnostik.

AIM: New evaluation of breast ultrasound based upon review of new literature comparing ultrasound and mammography. METHOD: Description and discussion of the published trials regarding breast imaging methods. RESULTS: Breast ultrasound is the preferable method in the case of a symptomatic patient (after clinical examination). In the case of a patient without symptoms (screening), breast ultrasound is ascribed a higher sensitivity for detecting breast cancer in women with dense breast tissue, women under the age of 50 and high-risk women. Mammographically occult cancers can be detected by sonography in 10 to 40 % of the cases depending on the patient's breast density and age. The mean size of cancers detected only by ultrasound is not significantly different to that only detected by mammography. The prevalence of breast cancers detected by ultrasound is approximately equal to the one detected by mammography, regarding the total number of examined patients. CONCLUSIONS: Breast ultrasound should be the preferred imaging procedure in the case of a palpable lump, leading to a definitive diagnosis itself or with an additional consecutive core needle biopsy. For women without symptoms, breast sonography should be mandatory and complementary to mammography in the case of breast density grade II (BI-RADS) or more. Application of breast ultrasound as a primary method or an alternative to mammography has not yet been evaluated sufficiently. It seems advisable in the case of women with dense breast tissue grade III and IV, women under the age of 50 and high-risk women. The implementation of breast ultrasound in this manner has to be checked by future trials.

Pharmacokinetics of azidothymidine and its major metabolite glucuronylazidothymidine in hemophiliacs coinfected with human immunodeficiency virus and chronic hepatitis C.

The increasingly reported cholestatic course of liver disease in hemophiliacs coinfected with human immunodeficiency virus (HIV) and hepatitis C (HCV) has been linked with impaired azidothymidine (AZT) metabolism in this patient group. Therefore, we compared the pharmacokinetics of AZT and its glucuronidated metabolite (glucuronylazidothymidine [GAZT]) in HIV/HCV-coinfected hemophiliacs without cirrhosis to HIV-infected patients without chronic hepatitis. Sixteen HIV/HCV-coinfected hemophiliacs without cirrhosis and six HIV-infected patients with negative hepatitis serology and normal liver transaminases received a single 100-mg oral dose of AZT. Subsequently, plasma concentrations of AZT and GAZT were measured during a 6-hour period by high-pressure liquid chromatography (HPLC). Blood samples were taken before and 30, 60, and 90 minutes and 2, 3, 6, and 8 hours after the intake of AZT. Pharmacokinetic parameters of AZT in HIV-infected patients with concomitant chronic hepatitis did not differ significantly as compared to patients without concomitant liver disease. GAZT half-life and mean residence time of GAZT, however, were significantly longer in HIV/HCV-coinfected hemophiliacs as compared to HIV-positive controls without hepatitis. In HIV-infected patients, underlying chronic hepatitis C does not require AZT dose adaptation. Yet despite normal oral clearance of AZT and GAZT, the increase of half-life and mean residence time of GAZT indicates a prolonged hepatic release of GAZT into the circulation of HIV-infected hemophiliacs with noncirrhotic hepatitis C.

Effects of standard breakfast on pharmacokinetics of oral zidovudine in patients with AIDS.

The influence of a standard breakfast on the single-dose pharmacokinetics of zidovudine (AZT) after oral administration of 100 and 250 mg of AZT was studied in 27 subjects with advanced human immunodeficiency virus infection (Centers for Disease Control stage IV). Concentrations of AZT and the 5'-glucuronide metabolite (GAZT) in serum and urine were measured by a high-pressure liquid chromatographic method. Pharmacokinetic analysis was done by an open one-compartment model as well as noncompartmentally. The results were summarized as medians with 50% confidence ranges because of the high degree of interindividual variability. Peak levels in plasma were moderately reduced after administration of 100 mg AZT in the nonfasting group (1.79 mumol/liter in the fasting group [F], 1.12 mumol/liter in the group that received breakfast [B]) and were markedly reduced after administration of 250 mg AZT (6.51 mumol/liter [F], 1.79 mumol/liter [B]). The terminal half-life in plasma was prolonged almost twofold after breakfast with 100 and 250 mg of AZT (100 mg, 36.4 min [F] and 51.6 min [B]; 250 mg, 35.3 min [F] and 63.6 min [B]). Recoveries (AZT and GAZT) in urine varied with both dosages, reflecting more a problem of accounting for the metabolite GAZT in urine than a relevant difference (100 mg, 115% [F] and 76.5% [B]; 250 mg, 71% [F] and 99.4% [B]). Our data suggest that absorption of AZT in human immunodeficiency virus-infected subjects is extremely variable, with a high degree of interindividual differences. Furthermore, breakfast had a marked influence on the absorption of AZT, suggesting that the drug should be taken in a fasting state.

Urinary caffeine metabolites in man. Age-dependent changes and pattern in various clinical situations.

In an exploratory study the 24-h urinary excretion pattern of caffeine and 14 of its major metabolites was studied in 32 volunteers (adults, adolescents and children), 14 patients either with end stage renal disease or liver cirrhosis, 7 heavy smokers and 27 patients on therapy with cimetidine, allopurinol, theophylline or phenytoin. Caffeine and its metabolites were quantified by UV-absorption after liquid/liquid-extraction and HPLC-separation, which ensured proper analysis of 1-methyluric acid. In adults the renal excretion of caffeine derivatives corresponded to an intake of 509 mg caffeine/day, with 1-methyluric acid as the predominant metabolite. About 69% of caffeine was degraded by the paraxanthine pathway, and theobromine- (19%) and the theophylline pathway (14%) were less important. The ratio of paraxanthine formation to urinary caffeine concentration (= clearance equivalent) was about 2.2 ml.min-1.kg-1 in adults, and the corresponding ratios for theophylline and theobromine were 0.43 ml.min-1.kg-1 and 0.59 ml.min-1.kg-1, respectively. As expected, caffeine degradation was impaired in patients with cirrhosis and was increased in persons who smoked heavily or who were on phenytoin therapy. The results document the possibility of noninvasively investigating gross differences in caffeine disposition by analysis of the urinary pattern of its metabolites.