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We sought to assess the impact of echocardiographic and hemodynamic grading of paravalvular leakage (PVL) after transcatheter aortic valve implantation (TAVI) on the prediction of 5-year mortality. PVL after TAVI is known to influence outcome after TAVI. Yet, present available data of long-term outcomes and especially the comparison of different modalities for measurement of PVL is little.We performed a retrospective single-center cohort study and compared the prognostic value of echocardiographic PVL grading as well as the aortic regurgitation index (ARI) pre- and post-TAVI. Univariable and multivariable Cox proportional regression analysis generated hazard ratios for mortality.A total of 464 patients underwent TAVI at our center between August 2012 and Decemebr 2014, with self-expandable CoreValve (11%) or balloon-expandable Sapien XT (47.4%) and Sapien 3 (41.6) valves. Overall 5-year mortality was 52.4% (243/464). Echocardiographic classes of PVL at discharge showed a significant (p = 0.002) association with 5-year mortality, mild PVL remained as an independent predictor for 5-year mortality in multivariable analysis (hazard ratio: 1.642 [95% confidence interval: 1.235-2.182]; p = 0.001). Grades of PVL as assessed during the procedure by ARI (below the previously defined cut-off of 25) did not show a significant association with 5-year mortality (p = 0.417 and p = 0.995, respectively).Even mild PVL assessed by echocardiography was an independent predictor for 5-year survival, whereas hemodynamic measurements did not help to identify PVLs that are relevant to 5-year survival.

Objectives We sought to assess angiographic, echocardiographic and hemodynamic grading of paravalvular leakage (PVL) after transcatheter aortic valve implantation (TAVI) with respect to prediction of 1-year mortality. Background Meaningful criteria for the severity of PVL are needed to allow intraprocedural guidance and patient management after TAVI. Methods We pooled the prospective TAVI databases of 2 German centers. During TAVI, PVL was assessed angiographically and by the aortic regurgitation index (ARI). ARI was calculated as ratio of the gradient between diastolic blood pressure and left ventricular end-diastolic pressure to systolic blood pressure times hundred. In addition, we performed transthoracic echocardiography before discharge. Results A total of 723 patients undergoing TAVI with self-expandable (20.9%) or balloon-expandable (79.1%) valves were included. Grades of PVL as assessed during the procedure by angiography or ARI (below the previously defined cut-off of 25) did not show a significant association with 1-year mortality (P = 0.312 and 0.776, respectively). One-year mortality was 15.7% (39/249) in patienths with an ARI

Although hypoglycaemia is a serious risk of intensive insulin therapy, studies on the accuracy of devices for self-monitoring of blood glucose (SMBG) include only a few values below 100 mg/dl. This study evaluated five SMBG devices in the normal range of blood glucose. In three separate series, capillary blood was taken from 207, 214 and 49 healthy subjects and was analysed with the SMBG devices and a laboratory method. Mean (± standard deviation) blood glucose values were 86 ± 13 mg/dl, 83 ± 12 mg/dl and 90 ± 16 in series 1-3. All measurements with SMBG devices differed significantly from the laboratory method. The relative deviation from the laboratory method was 5.5% (2.4-10.5%, median and interquartile range) for Accutrend®, 7.1% (3.6-12.6%) for Precision QID®, 7.5% (3.7-13.7%) for Accu-Chek III®, 14.1% (6.2-22.2%) for Companion 2® and 15.2% (10.3-21.3%) for One Touch II® (p < 0.05). In conclusion, this study shows important differences in the accuracy of five SMBG devices in the normoglycaemic range. Accutrend® and to a lesser degree - Accu-Chek III® and Precision QID® obtained better results and can be recommended for SMBG in patients treated with intensive insulin therapy.

Stacked layer sequences of InP-based HBT and HEMT are of interest for today's (OC-768) and tomorrows (OC-3072, 100 Gbit Ethernet) communication standards. The better low noise performance of the HEMT can be combined with the driver capability of the HBT while also a PIN-photodiode can be provided by the HBT base-collector-diode. However this results in a complex procedure for MOVPE growth process development. For a reliable fabrication of complex radio frequency (opto-)electronic circuit applications a quantitative InP process technology control is necessary starting at the level of device epilayer stacks. In this report the detailed characterization of stacked InP/(InGa)As:C HBT and InP/(InGa)As HEMT layer sequences is carried out by non-destructive X-ray analysis. Based on X-ray measurements in 004- and 002-reflection a detailed analysis of complex device layer stacks is purposed. As a result, an automatic calculation of layer parameters, e.g. thickness and composition is possible, reducing the turn-around time for the statistical process control (SPC).

InP-based high electron mobility transistors (HEMTs) are preferable for 40 GHz applications and beyond due to their low noise figure and the achievable high frequencies. We will report on the MOVPE growth of the required epitaxial InAlAs layers using the liquid precursors tertiarybutylarsine (TBAs) and ditertiarybutylsilane (DitBuSi). The Si, O and C concentrations of the InAlAs as function of the growth conditions will be discussed and it was observed that DitBuSi getters oxygen species and is the main unintentional carbon source for Si–InAlAs. Fabricated HEMTs show maximum oscillation frequencies f max of 210 GHz. Further data on material characteristics, uniformity and device performance will be discussed.

Quantum-effect devices utilizing resonant tunneling are promising candidates for future nano-scale integration. Originating from the technological progress of semiconductor technology, circuit architectures with reduced complexity are investigated by exploiting the negative-differential resistance of resonant tunneling devices. In this paper a resonant tunneling device threshold logic family based on the Monostable-Bistable Transition Logic Element (MOBILE) is proposed and applied to different parallel adder designs, such as ripple carry and binary carry lookahead adders. The basic device is a resonant tunneling transistor (RTT) composed of a resonant tunneling diode monolithically integrated on the drain contact layer of a heterostructure field effect transistor. On the circuit level the key components are a programmable NAND/NOR logic gate, threshold logic gates, and parallel counters. The special properties of MOBILE logic gates are considered by a bit-level pipelined circuit style. Experimental results are presented for the NAND/NOR logic gate.

The cure rate of patients with germ cell cancer of the testis has considerably improved since the introduction of cisplatin based chemotherapy. Because these patients are in their reproductive years and because some of them will be infertile after treatment, the effects of cytotoxic treatment on gonadal function are investigated by hormonal evaluations.In a transversal trial, luteinizing hormone, follicle-stimulating hormone and testosterone were determined radioimmunologically in serum samples of 232 patients with germ cell tumors after unilateral orchiectomy (patient age 18 to 64 years) up to 153 months after chemotherapy. Additionally, 51 of these patients were investigated in a longitudinal trial before and up to 5 years after chemotherapy. All patients received at least 2 courses of different cisplatin based chemotherapy regimens: cisplatin/vinblastine/bleomycin, cisplatin/vinblastine/bleomycin/ifosfamide, cisplatin/etoposide/bleomycin, cisplatin/vinblastine/bleomycin/ifosfamide/etoposide. Additionally, 11 patients with germ cell tumors (age 22 to 38 years, stage I) were investigated within the first year after orchiectomy and retroperitoneal lymphadenectomy but without chemotherapy.In the transversal trial, 24 of 73 patients investigated during the first year after chemotherapy showed elevated luteinizing hormone concentrations, 5 had subnormal serum testosterone and 65 had elevated serum follicle-stimulating hormone, reflecting spermatogenesis deficits. In 28 patients studied longer than 8 years after chemotherapy (median followup 8.5 years, range 8.0 to 12.6), luteinizing hormone increased after chemotherapy and 60 months after treatment, and follicle-stimulating hormone was elevated in 1 patient, follicle-stimulating hormone was increased in 18 and testosterone was subnormal in 1. Patients without chemotherapy treatment showed gonadotropin and testosterone within normal range and 3 patients had elevated serum follicle-stimulating hormone. In the longitudinal study, mean serum luteinizing hormone plus or minus standard deviation (3.45 +/- 0.05 IU/l.), follicle-stimulating hormone (7.79 +/- 0.13 IU/l.) and testosterone (18.6 +/- 0.17 nmol./l.) were within the normal range before chemotherapy; serum follicle-stimulating hormone was still significantly elevated (16.9 +/- 0.71 IU/l., 19 cases, p0.001). Mean luteinizing hormone and testosterone levels were within the normal range, but 60 months after therapy the testosterone-to-luteinizing hormone ratio was still lower than before treatment (p0.05).In patients with germ cell tumors, a compensated insufficiency of the function of the Leydig cells was still observed up to 60 months after chemotherapy. Of these patients 68% showed elevated follicle-stimulating hormone levels, which reflected a functional insufficiency of the Sertoli cells with impaired spermatogenesis. This study shows that impairment of germinative functions is more severe and protracted than the impairment of the endocrine functions.

Adrenomyeloneuropathy (AMN) is a disorder due to a disturbance in the peroxisomal beta-oxidation of saturated very long chain fatty acids. It is characterized by symptoms of the nervous as well as the endocrine systems, especially the adrenal cortex and the gonads. We investigated the testicular function in 49 male AMN patients aged 36.2 +/- 1.5 years (range, 18.5-59 years). Twenty-four of these patients were suffering from adrenocortical insufficiency. Twenty-five AMN patients showed neurological symptoms without 'Addison's disease'. To register the frequency and the degree of gonadal impairment, LH and FSH, testosterone, free testosterone and inhibin-B were determined. Gonadotropin concentrations were significantly higher in AMN patients than in healthy controls (LH, 8.0 +/- 1.2 vs 2.77 +/- 0.11 IU/l; FSH, 10.1 +/- 1.6 vs 4.0 +/- 0.17 IU/l; P < 0.001). Serum LH was elevated in 31 patients (63.3%); 28 patients (57.1%) showed elevated serum FSH indicating deficient spermatogenesis. Mean testosterone did not differ significantly between patients and healthy controls, but mean free testosterone was significantly lower in patients than in controls (16.3 +/- 1.0 vs 28.5 +/- 1.68 pg/ml, P < 0.002). Inhibin-B concentrations did not differ between AMN patients and healthy men. The testosterone/LH ratio reflecting an impairment of the Leydig cells was significantly lower in AMN patients than in controls (P < 0.01). An impairment of the Leydig cells and/or of the Sertoli cells was evident in 81.6% of AMN patients. Twenty-one of thirty-nine patients (53.8%) admitted erectile dysfunction. These data indicate that endocrine dysfunction in AMN is not only confined to adrenocortical functions, but testicular dysfunctions also frequently occur, thus permitting the term 'adreno-testiculo-myelo-neuropathy'.

Intermixing of an (InAs)n/(GaAs)m short period strained layer superlattice (SPSSL) is analyzed. Lattice matched (n ≈ mm) and indium rich (n > m) superlattices have been prepared by molecular beam epitaxy in order to provide a ternary InxGa1 − xAs channel in InP-HFET with a reduced alloy scattering as theoretically predicted. For the optimization the interface intermixing of highly strained heterostructures was investigated using high-resolution double-crystal X-ray diffractometry combined with computer simulations. A method of modelling imperfections in semiconductor heterostructures was introduced to perform the fit between the simulated and measured data in an objective manner. The key steps of this method are (i) the sensitivity analysis of experimental diffraction curve details with respect to imperfections, and (ii) the development of objective error criteria. The result of the modelling process enables a quantitative and objective determination of the intermixing at InAs/GaAs interfaces in relation to the molecular beam epitaxy (MBE) growth parameters.

Although clinical and experimental evidence favours early enteral feeding in the critically injured, provision of such enteral feeds can be difficult. Gastric feeds are often not tolerated and may lead to aspiration. An intolerance of gastric feeds leads to a cumulative energy and protein deficit and may result in the initiation of expensive parenteral nutrition (TPN). An alternative and under-utilized technique to ensure enteral access in trauma victims is the insertion of a transpyloric (nasojejunal) feeding tube during emergent laparotomy. We have employed this method of enteral access with success. In the following report, we describe this technique, provide an illustrative case with a cost comparison between nasojejunal feeds and TPN, present the rationale for such a mode of enteral access and outline the indications and contraindications. Enteral access by the intra-operative insertion of a transpyloric feeding tube allows immediate/early enteral feeding that is easy, safe, reliable and inexpensive.

Die Serumkonzentration der neuronspezifischen Enolase (NSE) wurde bei 126 Patienten mit malignem Melanom (MM, Stadium I / II: n=80; Stadium II:n = 23; Stadium IV:n = 23) radioimmunologisch bestimmt. Erhohte NSE-Konzentrationen (Schwellenwert: > 12, 5 μ/L) fanden sich bei 12, 5 % der Patienten mit MM im Stadium I / II, 13. 0 % im Stadium II und bei 39, 1 % im Stadium IV. In der Langzeit-Verlaufskontrolle bei 20 Patienten im Stadium II / K zeigte die NSE-Serumkonzentration eine Ubereinstimmung mit der Tumoraktivitat. Bei 6 Patienten zeigte sich unter der Therapie ein Abfall erhohter NSE-Werte als Zeichen einer Tumorregression. Das Ausbleiben eines signifikanten Abfalls oder gar ein Anstieg wies in 86, 7 % (13/15) der Falle auf eine Tumorprogression hin. Ein signifikanter Anstieg von NSE wurde bei 6 Patienten prafinal gesehen. Daraus last sich folgern, das NSE fur die Primardiagnostik des malignen Melanoms aufgrund der niedrigen Sensitivitat als Tumormarker ungeeignet ist; jedoch erscheint eine NSE-Bestimmung bei Patienten mit malignem Melanom im Rahmen einer Verlaufskontrolle sinnvoll.

Opioids have an inhibitory effect on sexual functions in both animals and humans. Twenty patients with idiopathic, nonvascular, nonneurogenic erectile dysfunction were treated with the opiate receptor antagonist naltrexone in a randomized, placebo-controlled, double-blind study for 8 weeks. Libido and frequency of sexual intercourse were not significantly altered, but early-morning erections increased significantly under naltrexone therapy. This response was not related to levels of androgens or gonadotropins, neither was it dose dependent. There was no change in any of the measured parameters under placebo. Further clinical studies with the substance should be conducted to evaluate its possible role in the oral treatment of male impotence.

This sensor-based approach for registration and stacking of electronic substrate sublaminates replaces pin-in-slot methods, yet does not require accurate automation equipment. Tests of a pilot workcell for this approach showed that the contact holes were consistently aligned to 2.5 /spl mu/m (3/spl sigma/), more than ten times better than the traditional mechanical method.

Brennemann W, Sommer L, Stoffel-Wagner B, Bidlingmaier F, Klingmüller D. Secretion pattern of immunoreactive inhibin in men. Eur J Endocrinol 1994;131:273–9. ISSN 0804–4643 Chronological changes in serum concentrations of inhibin, a gonadal glycoprotein hormone, were studied in healthy male volunteers (age 24–27 years). Secretion profiles of immunoreactive inhibin (ir-inhibin) were compared with those of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. Blood samples were collected every 15 min for 24 h. Serum inhibin concentrations were measured by a two-site immunoenzymatic assay with antibodies raised against distinct epitopes of the recombinant 1–32 amino acids of the α-subunit of human inhibin. The normal range for men was 0.79–3.1 U/l × 10−3, the sensitivity of the assay was 0.1 U/l × 10−3 (cv: within-assay, 6.8%; between-assay, 8.2%). Luteinizing hormone and FSH were measured by immunoradiometric assay and testosterone by radioimmunoassay. Secretion profiles of inhibin and testosterone were tested for diurnal variations by cosinor rhythmometry. Highest ir-inhibin concentrations were observed in the morning at 08.00 h, with peak values of 2.45–3.20 U/l × 10−3. During the evening and the night, ir-inhibin levels were relatively low; lowest concentrations were observed between 01.00 h and 02.00 h at night: 1.20–1.86 U/l × 10−3. Highest testosterone levels were observed in the morning (20.5–36.6 pmol/I), lowest concentrations were detected at night (7.35–12.6 pmol/l). Cosinor rhythmometry supported the suggestion that there is a clear circadian secretion of ir-inhibin and testosterone, respectively. The secretion pattern of ir-inhibin was analyzed by the Cluster pulse analysis computed algorithm, which identified four to seven inhibin pulses per day, depending on the person under observation. A significant correlation could be observed between median testosterone and ir-inhibin concentrations (r = 0.449, p < 0.001). In conclusion, ir-inhibin and testosterone in healthy male volunteers follow a clear diurnal rhythm. Moment to moment changes of ir-inhibin can be observed in all secretion profiles investigated. A probable physiological role for pulsatile inhibin secretion is not yet clarified. Dietrich Klingmüller, Institut für Klinische Biochemie, Universität Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany

In vitro studies have shown that the Sertoli cell is the primary source of inhibin in the male. We measured immunoreactive inhibin with a new two-site immunoenzymatic assay in the plasma of 92 men: 40 normal men, 7 patients with germinal cell cancer after unilateral orchidectomy and 45 patients with the same disease following unilateral orchidectomy and subsequent chemotherapy based on cisplatin. Normal men had inhibin levels of 1.77±0.09 U/l × 10−3 (mean±sem). Seven patients after unilateral orchidectomy had inhibin concentrations within the lower normal range (1.23±0.22 U/l × 10−3). Forty-five patients were investigated in a cross-sectional study up to 102 months after completion of chemotherapy. Inhibin levels were within the normal range in 25 patients (1.76±0.114 U/l × 10−3); 18 patients had significantly lower inhibin levels (0.48±0.05 U/l × 10−3, p−3). The proportion of patients with normal and subnormal inhibin was not dependent on the time that elapsed after completion of chemotherapy or on the chemotherapy combination. There was no correlation between immunoreactive plasma inhibin and LH, FSH, testosterone or sperm count. The decrease in inhibin concentrations after chemotherapy may indicate long-term damage to Sertoli cells in some of the patients.

A 1550-nm coherent receiver with a LiNbO3 optical hybrid and balanced photoreceivers integrated in a single compact package is reported. Frequency response of the integrated receiver and bit-error-rate measurements of optical PSK signals are described.

High-frequency vertical PIN detectors with highly p-type doped InGaAs basis layer were investigated. Reducing the PIN area and series resistance together with the thickness of the undoped drift region results in f3dB corner frequencies of up to 120 GHz. In addition, the vertical PIN concept reveals several advantages compared to waveguide PINs like the possibility to build two dimensional detector arrays and it is perfectly suited for monolithically integrated opto-electronic receiver ICs (OEIC). Further PIN and OEIC results will be presented.

Carbon doped InP/(InGa)As Heterostructure Bipolar Transistors (HBT) are of interest for today's (OC-768) and tomorrow's (OC-3072, 100 Gbit Ethernet, UMTS) communication standards. For a reliable fabrication of these complex radio frequency (opto-)electronic circuits, a quantitative InP process technology control is necessary starting at the level of device epi-layer stacks. In this paper the quantitative characterization of an InP/(InGa)As:C HBT is carried out by non-destructive X-ray analysis. Based on X-ray measurements in 004- and 002-reflection, a detailed analysis of complex device layer stacks is purposed. As a result, an automatic calculation of layer parameters, e.g. thickness and composition is possible, reducing the turnaround time for statistical process control (SPC).

An experimental system that can accurately align and place SMDs (surface mount devices) on a printed circuit board is described. Features of the system are fine positioning and endpoint sensing after an IBM 7576 robot coarsely aligns the SMD to its target. Fine positioning is done using a customer-designed micropositioning device. The endpoint sensor is a single camera vision system that by image analysis determines the alignment error of the SMD to the board. System performance was evaluated by placing SMDs of 100 leads with 25 mil lead spacing on a board. The alignment error is less than 0.5 mil and 0.015 degrees , independent of feeder and board position error or robot repeatability. The average cycle time is less than 10 s. >

Special-purpose sensors and hybrid mechanical systems have been developed to assemble advanced electronic circuits. State-of-the-art robot systems that are used for electronic assembly and accuracy requirements for the developing surface mount technology are reviewed, showing the need for improved robot positioning capability. Examples of laboratory experiments that demonstrated successful precision assembly or testing using an ordinary robot, a micropositioner, and an optical sensing system are given. These involve fiber-optic sensing, machine-vision endpoint sensing, and hybrid tactic-vision endpoint sensing. >

For simulation of digital circuits realized in Direct Coupled FET Logic (DCFL) using depletion-type as well as enhancement-type Heterostructure-Field Effect Transistors (HFET) a consistent model that is able to describe both types of transistors is necessary. The developed analytical PSPICE model takes into account all relevant intrinsic and parasitic effects. This model can be used for dc- as well as rf-simulations and is scaleable with respect to gate-width as well as gate-length.

Assembly accuracies of 0.05-0.1 mm, needed for electronic product manufacture, are attainable with current automated manufacturing equipment. Aggressive electronic system designs will require manufacturing accuracies in the range of 0.005-0.01 mm. A system and strategy is described here to fabricate circuit boards requiring alignment accuracies of 7.5 /spl mu/m using existing automation equipment with enhancements and typical manufacturing line fixtures. The system, configured as a pilot workcell, consisted of an IBM 7576 coarse positioning robot, a fine positioning manipulator, an optical sensing system and a unique bracing method to reduce environmental disturbances. The strategy was to use a coarse/fine placement technique with sensing to align, stack and bond individual test laminates with patterns of 100 /spl mu/m holes. The results showed that pairs of holes were consistently aligned to 2-5 /spl mu/m which surpasses the 7.5 /spl mu/m manufacturing requirement. >

This paper describes the InP-based HFET technology for the implementation of high bitrate logic gates. A novel logic gate configuration is presented based on depletion mode HFETs (DHFET) using a nonlinear negative feedback (NNFB) for optimized high speed operation. The NNFB increases the switching speed of the gates while reducing the logic HIGH output level. The functionality of this logic design approach is demonstrated in InP with an 11-stage inverter chain and an output buffer. The realization of a ring oscillator and an edge-triggered D-flip-flop are currently in progress.

We have developed a new concept for an optoelectronic frontend receiver at 0.85 /spl mu/m wavelength. A GaAs-PIN photodiode is coupled to a Permeable Junction Base Transistor (PJBT). The PJBT is a vertical Junction Field Effect Transistor with a homoepitaxial, heavily p-doped gate whose n-doped GaAs channel is selectively grown. Its layer structure incorporates two p-i-n doped layer structures, so it fits ideally to an integration with a PIN photodiode. The fabrication of the integration is described and results of the single devices, both DC and RF measurements, are presented. The performance of the first integrated receiver show the usefulness of this concept for Optoelectronic Integrated Circuits (OEIC) at bitrates of more than 1 Gbit/s.

Planar linear motors, e.g. Sawyer motors, operate in an open-loop stepping-manner. This mode of operation makes them: 1) susceptible to loss of steps, 2) unable to reject external disturbances, 3) unable to provide controlled forces, and 4) unable to provide high stiffness. These limitations, in turn, restrict their usefulness in a wide range of robotic applications. Suitable position sensing and control technology, when added to such motors, can to a large degree eliminate these problems. In this paper we present two new sensor technologies for planar motor systems: one uses an AC magnetic technique, the other uses an optical fluorescence technique. The magnetic sensor has achieved 1 /spl mu/m position resolution and is compact and easy to fabricate. The optical fluorescence sensor has the advantage of complete insensitivity to nearby motor fields. Either technology has the potential to greatly improve future robotic systems that are based on planar linear motors.

A pseudo dynamic logic family is developed on InP-substrates based on the MOBILE concept. The conventional HFET as input terminal is replaced by a monolithically integrated series combination of a HBT and a RTD forming a RTBT. This combination enables a logic function defined by the RTD area only. The HBT provides a robust enhancement type operation, although for full level compatibility a buffer inverter is still necessary. A novel distributed clocking scheme is developed. The feasibility of this logic concept is experimentally verified and an OR gate is discussed in detail.

The technology of resonant tunneling device logic circuits using a modified monostable-bistable transition logic element (MOBILE) is presented. A nanoelectronic circuit architecture based on an improved MOBILE threshold logic gate is used. The improvements of the basic MOBILE are motivated from the circuit design point of view, and comprise a separate power supply and clock, a dual threshold voltage process, and on-chip clock delay lines. The demonstrator circuit is a pipelined one-bit full adder on an InP-substrate. SPICE simulations are carried-out in order to prove the functionality and to evaluate tolerable clock and supply voltage fluctuations in comparison to device parameter feasibility.

This paper presents the performance of an 11-stage ring oscillator for high speed digital circuits using a gate configuration with nonlinear negative feedback (NNFB). An additional transistor is introduced into the switching path of buffered FET logic (BFL) gate to reduce the logic HIGH level, thus limiting the logic swing. As the result, the switching speed of the circuits is improved by about 50% compared to conventional BFL gates, while maintaining almost the same power consumption. The performance of this logic design approach is demonstrated by an e-beam written 11-stage ring-oscillator using InP-based depletion-type heterostructure field effect transistors (DHFET). The oscillation frequency is 3.36 GHz corresponding to a delay time of 13.5 ps per gate.

Adrenomyeloneuropathy (AMN) represents a milder form of X-linked adrenoleukodystrophy (ALD), the most frequent peroxisomal disorder. The disease is characterised by an abnormal accumulation of saturated, very long chain, fatty acids, because of altered peroxisomal beta-oxidation that concomitantly leads to demyelination in the central and peripheral nervous systems. ALD shows a highly variable phenotypic expression and extensive mutation analysis in ALD patients has failed to establish a genotype-phenotype correlation, even in the presence of the same ALD-gene defect. Therefore, we have looked for a relationship between the molecular lesion and the age of onset in 19 patients with a well-classified clinical course of AMN. The nearly complete novel spectrum of ALD gene mutations identified has revealed no obvious correlation between the type of mutation and age of AMN onset in this small series. However, intrafamiliar concordance could be observed with respect to the occurrence of adrenocortical insufficiency. This supports the idea of one (or more) additional gene(s) contributing to the phenotypic expression of ALD.