Measures of hippocampal volumes, diffusion and 1H MRS metabolic abnormalities in temporal lobe epilepsy provide partially complementary information.

We assessed whether interictal measures of hippocampal volume, hippocampal diffusion and metabolic abnormalities yield correlated or complementary information about hippocampal pathology in patients with temporal lobe epilepsy (TLE). Volumes, apparent diffusion coefficients (ADC) and ratios of N-acetyl-aspartate (NAA) to Creatine/Phosphocreatine (Cr) and Choline (Cho) were measured from each hippocampus during one magnetic resonance imaging (MRI) session in patients with TLE. Structural MRI showed unilateral hippocampal sclerosis (HS) in 13 patients and was normal in the remaining nine patients. Pearson's correlation (two-tailed) between ADC values and NAA/(Cr + Cho) ratios was significant (P = 0.04, r = -0.45) for the hippocampus ipsilateral to the epileptogenic zone as determined on the basis of interictal and ictal scalp EEG recordings. This finding was driven by a very high correlation between the two measures in the presence of HS (P < 0.001, r = -0.96). Furthermore, ipsilateral ADC values but not NAA/(Cr + Cho) ratios were correlated with disease duration (P = 0.001, r = 0.67). Hippocampal volumes did not correlate with either ADC values, NAA/(Cr + Cho) ratios or disease duration. These data suggest that hippocampal volumes, NAA/(Cr + Cho) ratios and ADC values capture partially complementary aspects of hippocampal pathology.

Structural basis for the high-affinity interaction of nidogen-1 with immunoglobulin-like domain 3 of perlecan.

Nidogen and perlecan are large multifunctional basement membrane (BM) proteins conserved in all metazoa. Their high-affinity interaction, which is likely to contribute to BM assembly and function, is mediated by the central G2 domain in nidogen and the third immunoglobulin (IG)-like domain in perlecan, IG3. We have solved the crystal structure at 2.0 A resolution of the mouse nidogen-1 G2-perlecan IG3 complex. Perlecan IG3 belongs to the I-set of the IG superfamily and binds to the wall of the nidogen-1 G2 beta-barrel using beta-strands C, D and F. Nidogen-1 residues participating in the extensive interface are highly conserved, whereas the corresponding binding site on perlecan is more variable. We hypothesize that a second, as yet unidentified, activity of nidogen overlaps with perlecan binding and accounts for the unusually high degree of surface conservation in the G2 domain.

Mapping of binding sites for nidogens, fibulin-2, fibronectin and heparin to different IG modules of perlecan.

Perlecan, a major basement membrane proteoglycan, has a complex modular structure designed for the binding of many cellular and extracellular ligands. Its domain IV, which consists of a tandem of immunoglobulin-like modules (IG2-IG15), is rich in such binding sites, which have been mapped to different modules obtained by recombinant production. Heparin/sulfatide binding was restricted to IG5 and shown to depend on four arginine residues that are close in space in beta strands B and E of the C-type IG fold. The nidogen-1 and nidogen-2 isoforms bind to IG3 with high affinity (K(d) approximately 10 nM). This interaction depends on the globular nidogen domain G2 and is crucial for the formation of ternary complexes with laminins. Two loops of IG3 located between beta strands B/C and F/G, which are spatially close, make a major contribution to binding. Fibronectin binding was localized to IG4-5 and fibulin-2 binds to IG2 and IG13-15 with different affinities. This implicates a complex cluster of heterotypic interaction sites apparently important for the supramolecular organization of perlecan in tissues.

Crystal structure and mutational analysis of a perlecan-binding fragment of nidogen-1.

Nidogen, an invariant component of basement membranes, is a multifunctional protein that interacts with most other major basement membrane proteins. Here, we report the crystal structure of the mouse nidogen-1 G2 fragment, which contains binding sites for collagen IV and perlecan. The structure is composed of an EGF-like domain and an 11-stranded beta-barrel with a central helix. The beta-barrel domain has unexpected similarity to green fluorescent protein. A large surface patch on the beta-barrel is strikingly conserved in all metazoan nidogens. Site-directed mutagenesis demonstrates that the conserved residues are involved in perlecan binding.

Endoscopically based endonasal and transnasal lasersurgery.

The endoscopically based endonasal and transnasal laser surgery is a surgical procedure, which offers the ENT-specialist a safe and effective method to cure or to improve a number of diseases of the upper and middle airways. Coagulative lasers are used in contact and noncontact mode. Their light is mainly absorbed by hemoglobin but rarely by water. The laser-tissue interaction is performed via flexible glass fibers. For the delivery of the laser beam we use specially designed applicator sheaths, which incorporate the endoscope, the laser fiber and the suction channel. The procedure is controlled online via the endoscopic image on the monitor ("video-endoscopy"). The patient suffers less trauma using this treatment compared to the standard endoscopic surgery and the procedure is much quicker. Pre- and post-operative rhinomanometric and rhinoresistometric measurements reveal that the air flow rate of the nose can be improved effectively.

[Initial studies of the application of the linear signal transfer theory in evaluating diaphanoscopic examinations exemplified by rheumatism diagnosis]. / Erste Untersuchungen zur Anwendung der linearen Signalübertragungstheorie in der Auswertung diaphanoskopischer Untersuchungen am Beispiel der Rheumadiagnostik.

Rheumatoid arthritis affecting the small joints--in particular the fingers--has advantageous geometry for the transmission of near-infrared (NIR) light. Examination of the optical properties of tissues has revealed that as a result of changes to the capsule and synovial fluid there is a considerable increase in photon scattering already in the early stages of the disease--in particular around 685 nm. This suggests the appropriateness of analysing the photon density profile resulting from punctiform irradiation of the joint. In a first approximation, the point spread function of transmitted photon density is confirmed to be proportional to a Gauss distribution, as suggested by Arridge. In accordance with the linear signal transfer theory, therefore, it is possible to establish a virtual transfer system described by a first-order differential equation. (The tissue optical conditions mu a << mu's and mu a = constant (mu a = absorption coefficient) were assumed). The parameter mu's (= reduced scattering coefficient) was determined by linear approximation of the Gauss distribution to the calculated or measured point spread function. For selected patient data, the mu's was determined in healthy and diseased finger joints (e.g. 10.1 cm-1 and 26.8 cm-1, respectively), and the results were in good agreement with those obtained experimentally.

Recombinant domain IV of perlecan binds to nidogens, laminin-nidogen complex, fibronectin, fibulin-2 and heparin.

Domain IV of mouse perlecan, which consists of 14 immunoglobulin superfamily (IG) modules, was prepared from recombinant human cell culture medium in the form of two fragments, IV-1 (IG2-9, 100 kDa) and IV-2 (IG10-15, 66 kDa). Both fragments bound to a heparin column, being eluted at ionic strengths either below (IV-2) or above (IV-1) physiological level, and could thus be readily purified. Electron microscopy demonstrated an elongated shape (20-25 nm), and folding into a native structure was indicated by immunological assay and CD spectroscopy. Solid-phase and surface plasmon resonance assays demonstrated strong binding of fragment IV-1 to fibronectin, nidogen-1, nidogen-2 and the laminin-1-nidogen-1 complex, with Kd values in the range 4-17 nM. The latter binding apparently occurs through nidogen-1, as shown by the formation of ternary complexes. Only moderate binding was observed for fibulin-2 and collagen IV and none for fibulin-1 and BM-40. Fragment IV-2 showed a more restricted pattern of binding, with only weaker binding to fibronectin and fibulin-2. None of these activities could be demonstrated for recombinant fragments corresponding to the N-terminal perlecan domains I to III. This indicates a special role for domain IV in the integration of perlecan into basement membranes and other extracellular structures via protein-protein interactions.

Normotensive offspring of hypertensive parents: no evidence of left ventricular diastolic dysfunction in a cross-sectional study.

Left ventricular filling alterations occur early in the development of systemic hypertension. We tested the hypothesis that alteration of diastolic filling might be present in a normotensive population with increased genetic risk for hypertension in the absence of increased left ventricular mass. In a blinded study we compared 31 lean, normotensive offspring of hypertensive parents having normal left ventricular mass (risk group) with 30 matched individuals without family history of hypertension (control group). Left ventricular diastolic function was assessed using Doppler echocardiography. Transmitral flow velocities showed no significant differences between the two groups. Peak early diastolic flow was 0.79+/-0.12 m/s and 0.79+/-0.13 m/s in the risk group and control group, respectively. Peak late diastolic flow was 0.44+/-0.08 in the risk group and 0.42+/-0.11 m/s in the control group. The ratio of early to late diastolic velocity was 1.85+/-0.32 and 1.94+/-0.37. The deceleration time of the early diastolic flow was identical in both groups: 138+/-24 ms and 138+/-23 ms. There was no significant prolongation of the isovolumic relaxation time in the risk group: 75+/-17 compared to 73+/-17 ms in the control group. Doppler measurements showed no correlation with left ventricular mass. We conclude that, in this cross-sectional study, young normotensive offspring of hypertensive parents do not exhibit Doppler echocardiographic signs of diastolic filling alteration in the absence of increased left ventricular mass.

Left ventricular structure and determinants in normotensive offspring of essential hypertensive parents.

OBJECTIVE: To assess whether currently normotensive offspring of essential hypertensive parents may have alterations in left ventricular mass (LVM) and function, and how these relate to some potential determinants. DESIGN AND METHODS: Echocardiographical indices of LVM (assessed by two-dimensional guided M-mode echocardiogram), 'clinic' blood pressure and daytime ambulatory blood pressure profiles, blood pressure responses to dynamic and isometric exercise testing, haematocrit, plasma and 24-h urinary electrolytes and catecholamines, and plasma angiotensin II were assessed on a defined Na+ intake in 31 normotensive lean sons of essential hypertensive parents (OHYP group) and 30 body mass index- and age-matched sons of normotensive parents (ONORM group). RESULTS: Clinic supine systolic blood pressure was higher in the OHYP than the ONORM group, but clinic diastolic and daytime ambulatory mean blood pressures, blood pressure loads and blood pressure during dynamic or isometric exercise did not differ significantly. LVM index (LVMI), interventricular septum thickness (IVST), posterior wall thickness (PWT), the IVST:PWT ratio, ejection fraction, fractional shortening, cardiac index and measured biochemical variables also did not differ significantly between groups. In the whole study population the LVMI correlated positively with the body mass index and negatively with plasma noradrenaline. CONCLUSIONS: In young lean men with one essential hypertensive parent and blood pressure still in the normal range, left ventricular structure and systolic function, as assessed by echocardiography, seem to be often unaltered and appropriate relative to the existing body habitus and blood pressure. Moreover, an early tendency for increasing resting blood pressure in genetically hypertension-prone humans may be more apparent under clinic than usual ambulatory conditions, whereas the blood pressure reactivity to physical stress seems to be largely normal at this stage.

[Cardiovascular causes of abnormal fatigability]. / Kardiovaskuläre Ursachen abnormer Ermüdbarkeit.

Excess fatigue is a common symptom of many chronic cardiovascular disorders with low cardiac output. Impairment of skeletal muscle function due to metabolic alterations seems to play a major role. In heart failure fatigue is a predominant symptom. It may be an early symptom on diseases with slow but progressive inhibition of blood flow, i.e. in constrictive pericarditis, pulmonary hypertension or mitral valve stenosis. Excess fatigue as a precursor of myocardial infarction is being discussed. Finally fatigue may be a limiting side effect of diuretic and beta-blocking agents.

Chronic ventricular electrograms: do steroid-eluting leads differ from conventional leads?

The aim of steroid-eluting leads is to reduce chronic pacing thresholds. Whether steroid-eluting leads also modify acute and chronic R wave amplitudes as well as R wave sensing of the pulse generator was investigated in 31 patients with a unipolar ventricular pacemaker. Four different leads were implanted: Two steroid-eluting leads with different electrode surface areas (8 mm2 and 5.8 mm2) and two conventional leads (Target Tip, Elgiloy lead). At implantation filtered R wave amplitudes, peak-to-peak values, and slew rates were measured by a pacing system analyzer. One year after implantation R wave amplitudes were directly determined from intracardiac electrograms and compared to the peak-to-peak data at implantation. Additionally, R wave inhibition was evaluated at a sensitivity setting of 5 mV. There were no differences among the four leads in respect to any of the parameters studied at implantation. At follow-up, no differences in R wave amplitudes were found leading to an appropriate sensing in all leads. Steroid-eluting leads did not differ from conventional leads and a smaller electrode surface area of 5.8 mm2 had no influence on ventricular electrogram. Together with a pacemaker with an input impedance of 37 kohms R wave sensing was a correct setting of 5 mV.

[Magnetic resonance imaging in rheumatology]. / Apport de l'imagerie par résonance magnétique en rhumatologie.

The authors report their experience with magnetic resonance imaging in rheumatology, established on more than 250 examinations. The method seems interesting for the study of discal and somatic spine diseases, and especially for the evaluation of tumor extension, the diagnosis of herniated disc, the diagnosis of spondylodiscitis, the exploration of the cervico-occipital joint. As compared to tomodensitometry, this method presents at the same time advantages and drawbacks. Peripherally, magnetic resonance imaging is useful for the exploration of bony tumors and evaluation of their extension. It gives excellent images of the knees and the hips where it seems to improve the results of tomodensitometry and bony scintigraphy in the diagnosis of osteonecrosis. It is likely that advances will broaden the scope of the indications and capabilities of this method.

[Heparin treatment. Comparison between intravenous and subcutaneous administration]. / Traitement héparinique. comparaison entre les voies d'administration intraveineuse et sous-cutanée.

48 patients with acute deep venous thrombosis of the lower limbs were treated with sodium heparin. In 23 patients heparin was injected subcutaneously (s.c.) twice a day and in 25 patients heparin was given by continuous intravenous perfusion (i.v.). Pain and edema disappeared after 8.7 days (s.c.) and 11.7 days (i.v.) respectively. One non fatal pulmonary embolism occurred in each group. A second venography was performed in 24 patients after 7 days of treatment and revealed no difference between the two groups. As judged by repeated thrombin time determination, anticoagulation was ineffective on at least one day in 39% of patients treated subcutaneously and in 60% of patients treated intravenously. The two pulmonary embolisms occurred in patients with ineffective anticoagulation. It is concluded that heparin may be used either intravenously or subcutaneously in the treatment of acute deep venous thrombosis. Thromboembolic complications occurred with both methods of treatment when anticoagulation was ineffective.

Domestication of Pulses in the Old World: Legumes were companions of wheat and barley when agriculture began in the Near East.

This article reviews the available information on the place of origin and time of domestication of the cultivated pea (Pisum sativum), lentil (Lens culinaris), broad bean (Vicia faba), bitter vetch (V. ervilia), and chickpea (Cicer arietinum). On the basis of (i) an examination and evaluation of archeological remains and (ii) an identification of the wild progenitors and delimitation of their geographic distribution, it was concluded that pea and lentil should be regarded as founder crops of Old World Neolithic agriculture. Most probably they were domesticated, in the Near East, simultaneously with wheats and barley (certainly not later than the sixth millennium B.C.). Bitter vetch shows a similar mode of origin. The evidence on the broad bean and the chickpea is much more fragmentary and the wild progenitors of these legumes are yet not satisfactorily identified. But also these two pulses emerge as important food elements in Bronze Age cultures of the Near East and Europe.