Optimization of localized 19F magnetic resonance spectroscopy for the detection of fluorinated drugs in the human liver.

Fluorine MR spectroscopy ((19)F MRS) is an indispensable tool for assessing the pharmacokinetics of fluorinated drugs. Since the metabolism of 5-fluorouracil (5FU), a frequently used cytotoxic drug, is expected to be different in normal liver and in tumor tissue, spatial localization is required for detection by MRS. In this study, three independent signal-to-noise ratio (SNR) optimizations were combined to enable chemical shift imaging (CSI) as a localization method in the detection of 5FU and its metabolites in tumor tissue. First, the hardware was optimized by using circularly polarized coils together with integrated preamplifiers. Second, the optimal pulse angle (Ernst angle) was determined on the basis of T(1) relaxation time measurements of 5FU. Finally, averaging of CSI phase-encoding steps was optimized by using the applied Hamming filter as a weighting function. The combination of these three methods enables the in vivo detection of 5FU and alpha-fluoro-beta-alanine (FBAL) by (19)F MRS, localized in three dimensions in tumor and liver tissue at a time resolution of 4 min at 1.5 Tesla.     

Nifedipine aggravates cyclosporine A-induced gingival hyperplasia

Gingival hyperplasia is a common side-effect of immunosuppression with cyclosporine A. Nifedipine is often used to control hypertension in kidney graft recipients. Analysis of gingival status in 106 children transplanted at our centre, and treated either with azathioprine, cyclosporine A or both, revealed significantly higher degrees of gingival overgrowth in those children receiving a combination of cyclosporine A and nifedipine compared with those children treated with cyclosporine A or nifedipine alone. Seven children undergoing gingivectomy at our centre over the past few years had received this combination. After a change in the antihypertensive regimen, avoiding long-term nifedipine medication, and improved dental care with chlorhexidine gel, we noted a reduction in the degree of gingival hyperplasia. In the majority of patients, nifedipine could be replaced by a single drug, usually hydralazine. We therefore recommend avoiding calcium channel blockers in the long-term management of hypertension in patients receiving cyclosporine.     

Post-renal transplant erythrocytosis in a child

We report the case of a 7-year-old boy who developed severe erythrocytosis 4 months after successful kidney transplantation, with a well-functioning graft. When the haematocrit rose above 60%, phlebotomy had to be performed once to twice a week in order to keep the haematocrit below 50%. A 3-month course of theophylline therapy did not influence the erythrocytosis significantly. There were 5 further patients with erythrocytosis out of 186 children who had undergone kidney transplantation at our centre.     

Peripheral blood neutrophil production of interleukin-1 receptor antagonist and interleukin-1β

Journal of Clinical Immunology - The objective of this study was to characterize interleukin-1 receptor antagonist (IL-1ra) and interleukin-1β (IL-1β) production by human peripheral blood...     

Characteristics of fibrinolytic enzyme release from human monocytes.

We have investigated further two patterns of neutral protease secretion previously described in cultured human monocytes. Freshly isolated or cultured monocytes were plated onto 125I-fibrin either with or without adherent immune complexes. Fibrinolysis was quantified in the presence or absence of added plasminogen. Freshly isolated monocytes cultured on plain fibrin produced fibrinolysis primarily through secretion of plasminogen activator (PA), while contact with adherent complexes induced the release of plasminogen-independent fibrinolytic enzymes. In vitro differentiation of monocytes led to altered enzyme release. PA secretion rose six-fold over the first 3 days of culture, then decreased. Plasminogen-independent enzyme release fell 70% after 24 hr of culture then declined no further. Whereas adherent complexes inhibited secretion of PA in freshly isolated cells, such complexes stimulated PA activity after 3 or more days of culture. PA secretion from freshly isolated monocytes was inhibited by cycloheximide, indicating a requirement for protein synthesis, and by cytochalasin B. PA secretion was also reduced by the local anaesthetics ethanol, octanol, or lidocaine, but was enhanced by propranolol. The reduced PA activity of freshly isolated monocytes cultured on adherent immune complexes was partially reversed by ethanol or propranolol, but not by cytochalasin B. The plasminogen-independent fibrinolytic activity or monocytes on adherent complexes was enhanced by cytochalasin B, but unaffected by cychloheximide suggesting that the enzymes were granule-associated. This secretion was reduced by preincubation with 8-Br-cAMP and methyl isobutyl xanthine and by the local anaesthetics examined.     

Low elementary movement speed is associated with poor motor skill in Turner's syndrome

The article aims to discriminate between 2 features that in principle both may be characteristic of the frequently observed poor motor performance in girls with Turner's syndrome (TS). On the one hand, a reduced movement speed that is independent of variations in spatial accuracy demands and therefore suggests a problem in motor execution. On the other hand, a disproportional slowing down of movement speed under spatial-accuracy demands, indicating a more central problem in motor programming. To assess their motor performance problems, 15 girls with TS (age 9.6-13.0 years) and 14 female controls (age 9.1-13.0 years) were tested using the Movement Assessment Battery for Children (MABC). In additionally, an experimental procedure using a variant of Fitts' graphic aiming task was used to try and disentangle the role of spatial-accuracy demands in different motor task conditions. The results of the MABC reestablish that overall motor performance in girls with TS is poor. The data from the Fitts' task reveal that TS girls move with the same accuracy as their normal peers but show a significantly lower speed independent of task difficulty. We conclude that a problem in motor execution is the main factor determining performance differences between girls with TS and controls.     

In vivo magnetic resonance imaging explorative study of ectopic bone formation in the rat

In animal studies of tissue engineering of bone, histology remains the standard for assessing bone formation. As longitudinal studies with this method are feasible only at the cost of large numbers of animals, we looked for an alternative. Therefore, demineralized bone matrix (DBM) and inactivated demineralized bone matrix (iDBM) implants were subcutaneously implanted in a rat. At 1, 3, 5, and 7 weeks postimplantation soft X-ray and magnetic resonance imaging (MRI) were done to monitor bone formation in the implants. At 7 weeks, the animal was killed and the implants were retrieved for histology. Our results showed that in vivo MRI is well suited to assess bone formation larger than 0.5 mm in diameter and to monitor the complete three-dimensional shape of the newly formed bone noninvasively and longitudinally. The MRI results matched well with the histology results obtained at 7 weeks. In contrast, X-ray imaging appeared inappropriate to monitor the bone formation process in DBM.     

False-negative prenatal diagnosis of restrictive dermopathy

Restrictive dermopathy is a rare autosomal recessive lethal skin dysplasia. It has been assumed that the characteristic morphologic abnormalities should allow a reliable prenatal diagnosis on fetal skin biopsies at about 20 weeks pregnancy. We report on a false-negative prenatal diagnosis. © 1992 Wiley-Liss, Inc.     

Classification of heart failure in population based research: An assessment of six heart failure scores

Several scores based on symptoms and signs have been developed to assess the presence of heart failure. The goal of this study was to compare six heart failure scores in non-hospitalised subjects and to determine their usefulness in population based research. The scores were applied to 54 participants of a population based study. All underwent a complete medical examination, including chest X-ray, electrocardiography and Doppler echocardiography. Using all information available, a cardiologist, unaware of the results of the scores, clinically classified participants as having no, possible or definite heart failure. Sensitivity, specificity, predictive values and receiver operating characteristics were calculated, using the cardiologist's assessment as a gold standard. The cardiologist judged definite or possible heart failure to be present in 17 persons. All scores had a high sensitivity for the detection of definite heart failure, whereas the study of men born in 1913 and Walma's score had the highest sensitivity for the combination of possible and definite heart failure. Gheorgiade's and the Boston score had the highest positive predictive values. In conclusion, five of the six scores we studied are broadly similar in the detection of heart failure. The men born in 1913 score relies heavily on the assessment of dyspnea, resulting in a relatively large number of false positives. Although the scores are useful in detecting manifest heart failure, objective measurements of cardiac function appear necessary to reduce the false positive rate and accurately detect early stages of heart failure.