The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr of 65 ml/min (median) was reduced to a nadir of 46 ml/min (p less than 0.01) during the first 2 h after infusion of cimetidine. GFR remained unchanged, and thus the fractional clearance of creatinine (CCr/CTh) was reduced from 1.43 (median) to 1.03 (p less than 0.01). CNa and the fractional excretion of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal tubular flow. This suggests that on-going cimetidine treatment must be taken into account when graft function is evaluated by the CCr alone.     

The spatiotemporal MEG covariance matrix modeled as a sum of Kronecker products

The single Kronecker product (KP) model for the spatiotemporal covariance of MEG residuals is extended to a sum of Kronecker products. This sum of KP is estimated such that it approximates the spatiotemporal sample covariance best in matrix norm. Contrary to the single KP, this extension allows for describing multiple, independent phenomena in the ongoing background activity. Whereas the single KP model can be interpreted by assuming that background activity is generated by randomly distributed dipoles with certain spatial and temporal characteristics, the sum model can be physiologically interpreted by assuming a composite of such processes. Taking enough terms into account, the spatiotemporal sample covariance matrix can be described exactly by this extended model. In the estimation of the sum of KP model, it appears that the sum of the first 2 KP describes between 67% and 93%. Moreover, these first two terms describe two physiological processes in the background activity: focal, frequency-specific alpha activity, and more widespread non-frequency-specific activity. Furthermore, temporal nonstationarities due to trial-to-trial variations are not clearly visible in the first two terms, and, hence, play only a minor role in the sample covariance matrix in terms of matrix power. Considering the dipole localization, the single KP model appears to describe around 80% of the noise and seems therefore adequate. The emphasis of further improvement of localization accuracy should be on improving the source model rather than the covariance model.     

Évaluation médico-économique du baclofène intrathécal chez les patients présentant une spasticité chronique sévère

A medicoeconomic evaluation of continuous intrathecal baclofen (Lioresal^®) infusion for symptomatic treatment of severe spinal spasticity was realised using a monocentric, comparative, retrospective approach where subjects were their own controls (n = 22). Study results confirm the efficacy of baclofen on symptoms, functional status of patients and on a non specific quality of life scale. Conversely, use of baclofen lead to a 67% increase of average annual costs of care for these patients and reaches around 173,500 French francs (~29,000 US$)/year. Such a cost seems to be acceptable with respect to clinical benefits. © 1998 Elsevier, Paris     

Binding of alpha-2-macroglobulin trypsin complex to human monocytes in culture

125I-labelled alpha 2-macroglobulin-trypsin (alpha 2MT) complex bound specifically to freshly isolated human blood monocytes at 4 degrees C but not to B or T lymphocytes, polymorphonuclear leucocytes, erythrocytes or thrombocytes. Binding of 12 pmol/l labelled alpha 2MT to freshly isolated monocytes was low. However, when monocytes were cultured in vitro, binding increased, reaching 10- to 20-fold higher specific binding by 2-4 weeks. Non-specific binding was absent. Considerable variations were observed in binding to monocytes from different cultures (individuals). The half-time of 125I-labelled alpha 2MT complex association to 14-days-old monocyte cultures was about 6 h at 4 degrees C. Dissociation of labelled complex after the addition of a saturing concentration of unlabelled complex was biphasic. About half of the labelled complex dissociated with a half-time of about 1 h, whereas the other half dissociated extremely slowly. At near steady state, half of the receptors were occupied at a complex concentration of about 200 pmol/l and Scatchard analysis showed that the data were adequately described by assuming one class of receptors. It is concluded that human monocytes express a marked increase in binding of alpha 2M complex when developing to macrophage-like cells in tissue cultures.     

The hemodynamic response of the alpha rhythm: an EEG/fMRI study

EEG was recorded during fMRI scanning of 16 normal controls in resting condition with eyes closed. Time variations of the occipital alpha band amplitudes were correlated to the fMRI signal variations to obtain insight into the hemodynamic correlates of the EEG alpha activity. Contrary to earlier studies, no a priori assumptions were made on the expected shape of the alpha band response function (ARF). The ARF of different brain regions and subjects were explored and compared. It was found that: (1) the ARF of the thalamus is mainly positive. (2) The ARFs at the occipital and left and right parietal points are similar in amplitude and timing. (3) The peak time of the thalamus is a few seconds earlier than that of occipital and parietal cortex. (4) No systematic BOLD activity was found preceding the alpha band activity, although in the two subjects with the strongest alpha band power such correlation was present. (5) There is a strong and immediate positive correlation at the eyeball, and a strong negative correlation at the back of the eye. Furthermore, it was found that in one subject the cortical ARF was positive, contrary to the other subjects. Finally, a cluster analysis of the observed ARF, in combination with a Modulated Sine Model (MSM) fit to the estimated ARF, revealed that within the cortex the ARF peak time shows a spatial pattern that may be interpreted as a traveling wave. The spatial pattern of alpha band response function represents the combined effect of local differences in electrical alpha band activity and local differences in the hemodynamic response function (HRF) onto these electrical activities. To disentangle the contributions of both factors, more advanced integration of EEG inverse modeling and hemodynamic response modeling is required in future studies.     

The effect of continuous subcutaneous insulin infusion on cardiac performance during exercise in insulin-dependent diabetics

To assess the effects of improved glycaemic control on the right and left ventricular ejection fraction (RVEF and LVEF), we performed radionuclide angiocardiography at rest and during exercise in nine insulin-dependent diabetics with a diabetes duration between 2 and 35 years (mean 12 years) and in 10 control subjects. The diabetics were investigated before and after 7 days' treatment with continuous subcutaneous insulin infusion (CSII). The diabetics had a significantly smaller rise in exercise-induced LVEF during normoglycaemia than in the hyperglycaemic state. In contrast to the control subjects, the diabetics, independent of glycaemic control, did not increase the end-diastolic volume and did not decrease the end-systolic volume during exercise. Our data indicate a preclinical abnormal left ventricular function in young diabetics without long-term diabetic complications. The dysfunction seems unrelated to changes in the loading of the heart and appears to be caused by decreased contractile reserve of the myocardium.     

Comparison between reference values for 201Thallium uptake and washout from the myocardium after exercise and after dipyridamole

Summary. A slow washout of ²⁰¹Thallium has a high diagnostic and prognostic value for coronary artery disease. The aim of the present work was to contribute with reference data on ²⁰¹T1 uptake and washout from the myocardium. With a quantitative method using circumferential profiles and interpolative background subtraction we performed ²⁰¹T1 myocardial imaging in two groups of subjects with a low probability of coronary artery disease. Washout in per cent is defined as (1-D/I) 100, where D is the delayed uptake rate and I the initial uptake rate. In group A (n=16) myocardial hyperaemia was induced by maximal exercise, in group B (n=15) by intravenous infusion of dipyridamole. In group A, the mean washout was 52%, and in group B it was 34% (P < 0.001). The delayed uptake rate D was significantly higher after dipyridamole, 58.4 cps, than after exercise, 44.5 cps (P < 0.05). There was no significant difference in I between the two groups. The findings regarding D and I explain that the washout is slower after dipyridamole than after exercise, as the mean D/I ratio was 0.48 in group A and 0.66 in group B (P < 00.1).     

The localization of spontaneous brain activity: first results in patients with cerebral tumors.

Objective: From EEG studies, it is known that structural brain lesions are accompanied by abnormal rhythmic electric activity. With the better spatial resolution of MEG, MEG dipole analysis can extend the knowledge based on EEG power spectra. This study presents the first results of a completely automatic analysis method applied to spontaneous MEG.Methods: Spontaneous MEG data of 5 patients with cerebral brain tumors and 4 controls were collected using a whole-head MEG system. Signals were bandpass-filtered with cut-off frequencies according to standard EEG bands. A moving dipole model was fitted to samples with at least twice the average sample power. Dipoles explaining 90% or more of the magnetic variance were projected onto a matched MR scan.Results: In controls, dipole distributions are symmetrical with respect to the mid-sagittal plane whereas distributions in patients often are asymmetrical to it. Dipoles describing gamma activity were located contralateral, and dipoles describing delta and theta activity were located ipsilateral to lesions.Conclusions: The automatic method gives plausible 3-dimensional information about generator foci of abnormal slow waves and other rhythms with respect to lesion foci and thereby adds physiological knowledge to that derived from EEG power spectra.