Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism

Three unrelated patients with excessive thymine-uraciluria due to dihydropyrimidine dehydrogenase deficiency are described. Excretory values (mmol/g creatinine) were: uracil 2.0-10.5, thymine 2.3-7.5, 5-hydroxymethyluracil 0.2-0.9. Orally administered (index patient) uracil and thymine were excreted for the greater part whilst dihydrouracil and S-dihydrothymine were mainly metabolised. Dihydropyrimidine dehydrogenase activities (nmol X h-1 X mg-1 protein) in leucocytes were 0.04, 0.01 and less than 0.01 in the patients, 0.31-1.66 in their parents, and 1.01-4.46 in controls (n = 4). The patients presented with a non-specific clinical picture of cerebral dysfunction.     

Automatic three-dimensional reconstruction and characterization of articular cartilage from high-resolution ultrasound acquisitions

Three-dimensional (3D) high-resolution ultrasonography has proved to be useful for in vitro assessment of cartilage remodeling due to osteoarthritis. The diagnosis is performed by computation of the mean thickness of the cartilage, which reveals hypertrophy or thinning, and by 3D reconstruction of the data, which provides essential information about the size, extent, and localization of the lesion. In both cases, preliminary segmention of the cartilage is necessary. This article proposes an algorithm for automatic segmentation of the cartilage from 3D ultrasonic acquisitions of the rat patella, which includes the detection of the cartilage surface and the cartilage/bone interface. The method was designed on the assumption of regularity and smoothness of the interfaces. The use of a global threshold was sufficient to separate the patella area from the background. The cartilage/bone interface was detected by selection of regions of interest (ROIs) encompassing the interface, followed by the detection of the interface within these ROIs using the graph theory. The method was applied to 162 samples. The detection accuracy was judged to be very good or good in 99% of the cases for the cartilage surface and in 86% of the cases for the cartilage/bone interface. The mean cartilage thickness value in the central part of the patella obtained from the automatic detection method was compared to that obtained manually. The coefficient of correlation between the two measurements was 0.92. These results show that our method is reliable. Thus, fast processing of a large number of acquisitions and a more complete analysis of the cartilage surface become possible.     

Circadian variation in ventricular tachycardia and atrial fibrillation in a medical-cardiological ICU

OBJECTIVE: To assess the diurnal distribution of ventricular tachycardia (VT) and atrial fibrillation (AF) in critically ill patients. DESIGN AND SETTING: Prospective observational study (episode-based design) in an eight-bed medical/cardiological ICU at a university hospital that also admits postoperative patients. PATIENTS: 98 consecutive patients with AF ( n=55) or ventricular tachycardia ( n=43). MEASUREMENTS AND RESULTS: There were a total of 218 arrhythmia episodes (83 AF, 136 VT). The time of arrhythmia onset was not evenly distributed. Circadian variation in VT but not AF onset was well represented by a sine wave function. Both VT and AF fibrillation showed a trough during the night. The distribution of VT and AF episodes did not differ significantly with or without analgosedation. CONCLUSIONS: In critically ill patients the onset of VT and AF over 24-h is nonuniformly distributed. In VT this circadian pattern of occurrence is well modeled by a sine wave function peaking between noon and 2 p.m. The circadian pattern is less clear for AF. The circadian variation is seen irrespective of the presence of absence of analgosedation for both arrhythmias.     

EMPHYSEMATOUS PYELONEPHRITIS RESPONDING TO MEDICAL THERAPY

We describe two type 2 diabetic patients with unilateral emphysematous pyelonephritis who responded to medical treatment alone. Escherichia coli was isolated in both patients. The presence of gas was confirmed early by ultrasound and CT scan of abdomen. Following treatment, good functional recovery was demonstrable in the affected kidneys by isotope renogram. We stress the need for early diagnosis of this condition and aggressive treatment with broad spectrum antibiotics.     

Extrapancreatic Glucagon and Glucagonlike Immunoreactivity in Depancreatized Dogs: A QUANTITATIVE ASSESSMENT OF SECRETION RATES AND ANATOMICAL DELINEATION OF SOURCES

The anatomical sites and the rates of extrapancreatic secretion of glucagon and of glucagon-like immunoreactivity (GLI) were assessed in dogs 2 h after pancreatectomy by catheterization of the gastrosplenic and mesenteric veins.     

An enzyme-linked immunosorbent assay for lactose synthase (galactosyltransferase) in serum and its application as a tumor marker in ovarian carcinoma

This assay for lactose synthase (galactosyltransferase, EC 2.4.1.22) in serum involves two sequential incubations: serially diluted standard or sample antigen is reacted with a fixed amount of antibody; unbound antibody is then adsorbed to wells of antigen-coated microtiter plates and determined by a second antibody directed against the first antibody and coupled to phosphatase. The standard curve is linear for galactosyltransferase concentrations of 10 to 600 micrograms/L. The within-assay CV of a serum sample was 9.3% (SD 4.1%), the between-assay was 3.8% (SD 2.4%). Serum galactosyltransferase concentrations computed from three different dilutions yielded CVs of 6.5% (SD 5.7%, n = 14). We evaluated the method's accuracy by recovery analysis and by comparing enzyme activity in serum with that of purified galactosyltransferase from human milk. The normal reference interval, as estimated from data on 27 healthy blood donors, was 60-436 micrograms/L (mean 224, SD 101 micrograms/L). We applied the assay to samples of serum from ovarian carcinoma patients grouped according to tumor burden. We also determined galactosyltransferase in ascites fluid and found these values useful for diagnosis, whereas determinations in serum may serve mainly for patient monitoring.     

Intrinsic and acquired forms of resistance against the anticancer ruthenium compound KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A)

KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A) is a metal complex with promising anticancer activity. Since chemoresistance is a major obstacle in chemotherapy, this study investigated the influence of several drug resistance mechanisms on the anticancer activity of KP1019. Here we demonstrate that the cytotoxic effects of KP1019 are neither substantially hampered by overexpression of the drug resistance proteins multidrug resistance-related protein 1, breast cancer resistance protein, and lung resistance protein nor the transferrin receptor and only marginally by the cellular p53 status. In contrast, P-glycoprotein overexpression weakly but significantly (up to 2-fold) reduced KP1019 activity. P-glycoprotein-related resistance was based on reduced intracellular KP1019 accumulation and reversible by known P-glycoprotein modulators. KP1019 dose dependently inhibited ATPase activity of P-glycoprotein with a K(i) of approximately 31 microM. Furthermore, it potently blocked P-glycoprotein-mediated rhodamine 123 efflux under serum-free conditions (EC(50), approximately 8 microM), however, with reduced activity at increased serum concentrations (EC(50) at 10% serum, approximately 35 microM). Moreover, P-glycoprotein-mediated daunomycin resistance could only be marginally restored by KP1019 in serum-containing medium, also indicating an influence of serum proteins on the interaction between KP1019 and P-glycoprotein. Acquired KP1019 resistance was investigated by selecting KB-3-1 cells against KP1019 for more than 1 year. Only an approximately 2-fold KP1019 resistance could be induced, which unexpectedly was not due to overexpression of P-glycoprotein or other efflux pumps. Accordingly, KP1019-resistant cells did not display reduced drug accumulation. Their unique cross-resistance pattern confirmed an ABC transporter-independent resistance phenotype. In summary, the likeliness of acquiring insensitivity to KP1019 during therapy is expected to be low, and resistance should not be based on overexpression of drug efflux transporters.     

Options for interventional heart catheterization in congenital heart disease

Parallel to the rapid advances in the surgical options in treating congenital heart defects pioneering innovations in interventional cardiology could establish alternative treatment to surgery for these patients. On the one hand there is a trend to interventionally cure simple heart defects, but on the other hand interventional procedures can often only support surgical treatment. This review gives a limited overview over the recent possibilities and problems of the interventional cardiology and therefore focuses on balloon dilatation of congenital valve or vessel stenoses, on device closure of intracardiac defects and on the implantation of stents for the enlargement of elastic or long stenoses.