Implementation of a new Cryopad on the diffractometer POLI at MLZ.

A new polarized neutron single crystal diffractometer POLI (Polarization Investigator) has been developed at the Maier-Leibnitz Zentrum, Garching, Germany. After reviewing existing devices, spherical neutron polarimetry has been implemented on POLI as a main experimental technique using a third-generation cryogenic polarization analysis device (Cryopad) built in cooperation between RWTH University and Institut Laue-Langevin. In this report we describe the realization and present the performance of the new Cryopad on POLI. Some improvements in the construction as well as details regarding calibrations of Cryopad and its practical use are discussed. The reliable operation of the new Cryopad on POLI is also demonstrated.

Structural phase transition and hydrogen ordering of TlH2PO4 at low temperature.

The crystal structure of TlH(2)PO(4) (TDP) has been studied at low temperature. The lattice parameters were derived from high-resolution X-ray powder diffraction in the temperature range between 8 and 300 K. A detailed crystal structure analysis of the antiferroelectric low-temperature phase TDP-III has been performed based on neutron diffraction data measured at 210 K on a twinned crystal consisting of two domain states. The structure model in the triclinic space group P\bar 1 is characterized by a complete ordering of all the H atoms in the asymmetric O-H...O hydrogen bonds. The phase transition from the ferroelastic TDP-II to the antiferroelectric TDP-III phase at 229.5 +/- 0.5 K is only slightly of first order and shows no detectable hysteresis effects. Its mechanism is driven by the hydrogen ordering between the partially ordered TDP-II state and the completely ordered TDP-III state. The polymorphism of TDP and the fully deuterated TlD(2)PO(4) (DTDP) is presented in the form of group-subgroup relations between the different space groups.

[Lipiwatch: a study of the treatment of dyslipidemias in Luxembourg]. / Lipiwatch: une étude du traitement des dyslipidémies au Luxembourg.

LIPIWATCH is an observational study which has been initiated for 6 months in Belgium and in Luxembourg in 1997 to evaluate if patients treated by lipid-lowering drugs could reach the recommendations of the EAS and NCEP II for LDL-C. 76 patients (31 men) with a mean age of 59.2 +/- 11.39 years were included. 96% of patients had at least one other associated cardiovascular risk factor. After 6 months of treatment, 33% of all patients and only 30% of patients with coronary heart disease or peripheral vascular disease or at least 2 other risk factors reached the recommendations of the EAS. 25% of all patients and only 20% of patients with known coronary heart disease reached the NCEP II recommendations. 55% of patients had a statin prescribed and 38% a fibrate. Mean total cholesterol and mean LDL-C was lowered by 20% and 19% after 6 months. These disappointing results confirmed an insufficient awareness by physicians and patients, inadequate dosages of drugs and a bad compliance by patients.

Weak relationship between symptom perception and objective hypoglycaemia-induced changes of autonomic function in hypoglycaemia unawareness in diabetes.

To assess the relationship between symptom perception and neurophysiological characteristics in hypoglycaemia unawareness, we investigated the awareness of symptoms, objective changes of autonomic function and counter-regulatory neuroendocrine responses to hypoglycaemia in intensively treated type I (insulin-dependent) diabetic patients with different degrees of hypoglycaemia unawareness. Hypoglycaemia (venous plasma glucose below 2.2 mmol/l) was induced with an intravenous insulin bolus in subjects with a history of repeated severe hypoglycaemia and hypoglycaemia unawareness (n = 10) and in a comparable group with good awareness of hypoglycaemia (n = 8). Autonomic symptoms, selected parameters of autonomic function and counter-regulatory hormones were assessed serially. Although hypoglycaemia was more pronounced in unaware patients (1.6 vs 2.0 mmol/l, P = 0.05), their induced adrenaline response was markedly impaired (delta adrenaline: 1.25+/-1.10 vs 2.55+/-1.46 nmol/l, P = 0.05). Astonishingly, differences between both patient groups in the course of autonomic function changes did not reach the level of significance (P = 0.35-0.92), although the unaware group reported markedly fewer autonomic symptoms, both neurogenic (P = 0.001) and neuroglycopenic (P = 0.04) than the aware group. This study indicates that in hypoglycaemia unawareness even extensive changes in autonomic function are not sufficient for the perception of hypoglycaemia and confirms that the central nervous system plays an important role in the awareness of hypoglycaemia.

Heart rate variability in isolated rabbit hearts.

The presence of heart rate variability (HRV) in patients with cardiac denervation after heart transplantation raised our interest in HRV of isolated, denervated hearts. Hearts from seven adult white ELCO rabbits were transferred to a perfusion apparatus. All hearts were perfused in the working mode and in the Langendorff mode for 20 minutes each. HRV was analyzed in the frequency domain. A computer simulated test ECG at a constant rate of 2 Hz was used for error estimation of the system. In the isolated, denervated heart, HRV was of random, broadband fluctuations, different from the well-characterized oscillations at specific frequencies in intact animals. Mean NN was 423 +/- 51 ms in the Langendorff mode, 406 +/- 33 ms in the working heart mode, and 500 ms in the test ECG. Total power was 663 +/- 207 ms2, 817 +/- 318 ms2, and 3.7 ms2, respectively. There was no significant difference in any measure of HRV between Langendorff and working heart modes. The data provide evidence for the presence of HRV in isolated, denervated rabbit hearts. Left atrial and ventricular filling, i.e., the working heart mode, did not alter HRV, indicating that left atrial or ventricular stretch did not influence the sinus nodal discharge rate.

Severe hypoglycaemia unawareness is associated with an early decrease in vigilance during hypoglycaemia.

To elucidate neurophysiological characteristics in hypoglycaemia unawareness, we investigated the relationship between electroencephalography (EEG) parameters of vigilance and awareness of various symptom categories early in response to hypoglycaemia in intensively treated diabetic patients with different degrees of hypoglycaemia unawareness. Hypoglycaemia (venous plasma glucose below 2.2 mmol/1) was induced with an intravenous insulin bolus in seven patients with insulin-dependent diabetes mellitus (IDDM) with a history of hypoglycaemia unawareness and repeated severe hypoglycaemia, as well as in a group of seven IDDM patients with good awareness of hypoglycaemia. Both groups were comparable in age, treatment strategy, glycaemic control and level of late complications. Basic cognitive performance and other symptom categories were estimated serially during a period of 2 h following the insulin bolus. A vigilance-controlled EEG was recorded continuously; its automatic analysis included the evaluation of vigilance indices. In the baseline prehypoglycaemic state, hypoglycaemia unaware patients showed higher initial vigilance (p = .05) than the aware group. Unaware patients reported fewer neurogenic (p = .002, mainly cholinergic, p = .009) hypoglycaemia symptoms during hypoglycaemia, and developed an impairment in cognitive performance over time (p = .002). EEG analysis indicated a more rapid decrease in vigilance after the hypoglycaemic stimulus for unaware patients than for aware patients. The lowering of plasma glucose to 3.06-3.89 mmol/l already induced a significant increase in delta and theta, as well as a decrease in alpha relative power only in the unaware group. Differences between groups with regards to the degree of deceleration were most pronounced early, during only slight hypoglycaemia, and topographically spread over central and parietal brain regions. Further lowering of plasma glucose induced an even more pronounced, abrupt increase in slow waves in unaware patients at higher plasma glucose levels than in hypoglycaemia aware subjects (for delta waves at 2.41 +/- 0.16 vs. 1.96 +/- 0.1 mmol/l, p = .04). This preceded the worsening of cognitive performance during hypoglycaemia in unaware patients by 19 +/- 3 min. Hypoglycaemia unawareness associated with previous unconsciousness is associated with- and may be the result of-an early hypoglycaemia-induced reduction in vigilance and an early EEG deceleration, which seems to be a teleologically effective measure for delaying eventual cerebral energy failure in hypoglycaemia.

Monitoring set-up for selection of parameters for detection of hypoglycaemia in diabetic patients.

Recurrent severe hypoglycaemia is often an unsolved problem in diabetic patients under intensified insulin treatment. As no reliable long-term stable blood glucose sensor has yet been developed, registration of other body function changes could help to detect severe hypoglycaemia. A measuring system is described, capable on the one hand of recording EEG, heart rate, peripheral pulse, skin temperature, respiratory movements, skin impedance and arterial blood pressure, and capable of registering plasma glucose, counter-regulatory hormones, symptoms and cognitive performance under experimental conditions during hypoglycaemia, on the other. In a clinical study involving both insulin-induced hypoglycaemia in healthy subjects and insulin-dependent diabetic patients, the practical value and the character of changes of the recorded parameters are investigated. Currently insensitivity to hypoglycaemia, impracticability, complexity or susceptibility to artefacts make use of most parameters unsuitable for hypoglycaemia prevention. It is believed, however, that future efforts could result in indirect registration of hypoglycaemia, including a qualified combination of different parameters, individual adaptation in accordance with particular responses of individual patients, together with new measuring and sensor techniques.

EEG topography during insulin-induced hypoglycemia in patients with insulin-dependent diabetes mellitus.

A group of young patients with insulin-dependent diabetes mellitus (n = 14; 8 men, 6 women; 33.1 +/- 8.9 years) were examined by topographic EEG mapping under normoglycemic and hypoglycemic conditions (glucose levels after intravenous insulin injection down to 32.6 +/- 7.6 mg/dl). From the clinical aspect, 7 of them had a good and 7 had a poor awareness of hypoglycemia. During hypoglycemia, a decrease in alpha activity (p < 0.05), an increase in delta (p < 0.05), and especially in theta activity (p < 0.05) were found. The most sensitive parameter was the alpha/theta ratio. In the range of slight hypoglycemia (50-60 mg/dl) the increase in delta and theta activity showed a topographic maximum in lateral frontal regions. During deep hypoglycemia there was a topographic maximum of slow frequencies in posterior parts of the brain (centrotemporal to parieto-occipital regions). The differences between the group with good and with poor awareness of hypoglycemia were most pronounced during slight hypoglycemia in C3, C4, and Pz (p < 0.05). At lower glucose levels group distinction was no longer possible. These EEG changes correspond to a temporary organic brain syndrome.

Monitoring of FES-induced muscle activity by continuous EMG-recording.

Functional Electrical Stimulation (FES) requires information on the stimulated muscle for adjustment of the stimulation current, avoidance of muscle fatigue during the conditioning period and long term follow-up. Several applications of chronical FES are in clinical practice, but a system for direct registration of muscle activity under FES still does not exist. In six sheep the right Latissimus Dorsi Muscle (LDM) and Thoracodorsal Nerve were exposed. Stimulation electrodes were applied to each nerve and 3 EMG-applied sensing electrodes were placed into each LDM. The LDM tendon was connected to a force transducer. Burst stimulation was applied and the amplitude was increased from 0 to 4 mA in steps from burst to burst. EMG (M-wave) was amplified and recorded continuously via modified instrumentation amplifier, oscilloscope and tape recorder. Isometric muscle tension was recorded using force transducer, A/D interface and PC. Continuous EMG-recording was performed in all cases. Simultaneous recording of muscle tension and EMG revealed a close correlation (IrI=0.95, p < 0.0001) between the muscle strength and amplitude of the M-wave. Continuous recording of the EMG seems to be a reliable method for direct monitoring of the stimulated muscle. Three intramuscular electrodes can provide enough information to monitor FES induced muscle activity.

[Noninvasive fetal pulse oximetry sub partu. Experiences with the Ohmeda Biox 3700 and the Baxter Asat 1000 Pulse Oximeter]. / Nichtinvasive fetale Pulsoximetrie sub partu. Erfahrungen mit dem Ohmeda-Biox-3700- und dem Baxter-Asat-100-Pulsoximeter.

In this study oxygen saturation was measured at the presenting part of the fetus during labour. We used two different reflectance sensors together with two different pulse oximeters. The Baxter Asat 100 displayed a 25% lower functional oxygen saturation of haemoglobin (SaO2) compared to the Ohmeda Biox 3700 pulse oximeter. The mean duration of application using the Ohmeda Biox 3700 together with an adapted finger sensor was 36 min (SD +/- 17 min), an effective measurement was achieved for 15 min (SD +/- 9 min). The mean duration of application using the Baxter Asat 100 together with a commercial Baxter reflex sensor was 88 min (SD +/- 96 min), an effective measurement was attained for 73 min (SD +/- 77 min).

Mediastinal Clear Cell Lymphoma-A Distinct Entity of B-Cell Derived Lymphoma as Shown by Immunotyping and Analysis of Gene Rearrangements.

Mediastinal clear cell lymphoma (MCCL) is regarded as a distinct subtype of Non-Hodgkin's-lymphoma. We have analyzed gene rearrangements of eight cases of newly diagnosed MCCL in order to verify their alignment to the B-cell lineage as suggested by immunotyping. The lymphoma cells shared a common immunophenotype which consisted of CD10-, CD19+, CD20+, and CD21-. Rearrangements of the heavy chain of the immunoglobulin gene were found in all eight cases studied. In contrast, the beta chain of the T-cell antigen receptor gene was not rearranged. No rearrangements of the kappa light chain gene were detected. There was no evidence for a t(14;18) or a t(8;14). In conclusion, MCCL seems to be a B-cell derived tumor, which is distinct from other known lymphomas both by its immunophenotype and genotype.

Detection of Minimal Residual Disease in Adult Acute Lymphoblastic Leukemia by Analysis of Gene Rearrangements and Correlation with Early Relapses.

While more than 75% of the adult patients with acute lymphoblastic leukemia (ALL) achieve a complete remission after treatment with intensive chemotherapy, about 40% of them relapse within five years. These relapses are probably due to residual leukemic cells. Gene rearrangements are used as markers of clonality and thereby monoclonal leukemic lymphoid cells can be detected with high sensitivity. In this study, we have applied the analysis of gene rearrangements to detect minimal residual disease in patients considered to be in complete remission. Serial bone marrow samples were studied in 35 patients before and four weeks after initiation of a standardized induction chemotherapy. Gene probes for the joining regions of the human immunoglobulin heavy chain and the constant regions of the human T-cell receptor ß-chain were used. In five of the 35 patients, the same gene rearrangements found before therapy persisted and indicated residual disease. Four of them relapsed within a median time of 10 weeks. Six of the 30 other patients without detectable gene rearrangements after induction therapy also relapsed, but median time to relapse was 30 weeks. Two of them had a relapse in the central nervous system without detectable bone marrow infiltration. Our data suggest that minimal residual disease, detected by analysis of gene rearrangements, is associated with a high early relapse rate. Analysis of gene rearrangements at the time of assessing the response to primary therapy seems to be of prognostic value in ALL and may contribute to a stratification of further therapy.