Reconstruction of wave front and object for inline holography from a set of detection planes.

We illustrate the errors inherent in the conventional empty beam correction of full field X-ray propagation imaging, i.e. the division of intensities in the detection plane measured with an object in the beam by the intensity pattern measured without the object, i.e. the empty beam intensity pattern. The error of this conventional approximation is controlled by the ratio of the source size to the smallest feature in the object, as is shown by numerical simulation. In a second step, we investigate how to overcome the flawed empty beam division by simultaneous reconstruction of the probing wavefront (probe) and of the object, based on measurements in several detection planes (multi-projection approach). The algorithmic scheme is demonstrated numerically and experimentally, using the defocus wavefront of the hard X-ray nanoprobe setup at the European Synchrotron Radiation Facility (ESRF).

Approaching the full octave: noncollinear optical parametric chirped pulse amplification with two-color pumping.

We present a new method to broaden the amplification range in optical parametric amplification toward the bandwidth needed for single cycle femtosecond pulses. Two-color pumping of independent stages is used to sequentially amplify the long and short wavelength parts of the ultrabroadband seed pulses. The concept is tested in two related experiments. With multi-mJ pumping pulses with a nearly octave spanning spectrum and an uncompressed energy of 3 mJ are generated at low repetition rate. The spectral phase varies slowly and continuously in the overlap region as shown with 100 kHz repetition rate. This should allow the compression to the Fourier limit of below 5 fs in the high energy system.

Octave wide tunable UV-pumped NOPA: pulses down to 20 fs at 0.5 MHz repetition rate.

Femtosecond laser pulses, which are tunable from 440 to 990 nm, are generated at MHz repetition rates by noncollinear parametric amplification (NOPA). The pulses have durations of 20 to 30 fs over the major part of the tuning range and a high energy stability of 1.3% (rms). The NOPA is pumped with ultraviolet pulses from the third harmonic of an ytterbium doped fiber laser system and seeded by a smooth continuum generated in bulk sapphire. The residual second harmonic is used to pump an additional NOPA, which is independently tunable from 620 to 990 nm. Interference experiments show that the two NOPA systems have a precisely locked relative phase, despite of being pumped by different harmonics with a random phase jitter. This demonstrates that the phase of pulses generated by optical parametric amplification does not depend on the pump phase.

Driving in Parkinson's disease - a health hazard?

BACKGROUND: The driving safety of Parkinson's disease (PD) patients has lately been questioned after several authors reported road accidents caused by sleep attacks in PD patients on dopaminergic medication. OBJECTIVES: To determine 1) whether PD patients in general and those on dopaminergic medication in particular are especially prone to cause severe road accidents and 2) whether there are PD symptoms or dopaminergic side effects with the potential to compromise driving safety. DATA SOURCE: Relevant articles were identified by electronic search of biomedical databases (1966-2002: MEDLINE, EMBASE, PASCAL, PUBMED), the Cochrane Controlled Trials Register, and reference lists of located articles. RESULTS: Despite frequent occurrence of potentially hazardous dopaminergic side effects (2-57 %) and disabling parkinsonian non-motor and motor disabilities (16-63 %), the two existing studies on accident rates suggest that PD patients are not more prone to cause road accidents than the rest of the population. Five further reports including 1346 patients and focusing on dopaminergically induced sleep attacks provided comparably low accident figures (yearly incidence: 0%-2%). Because of low figures meta-analysis was intended but finally deemed inappropriate as the methodology of included studies varied greatly and was frequently flawed. CONCLUSION: Further prospective community-based well designed studies on accident risk in PD patients are needed to provide evidence based driving recommendations.

Fracture properties of the human mandible.

A total of seven human mandibles were struck to breaking point under standardised conditions using a pendulum. The cortical deformation for two impact directions was measured with strain gauge strips located at eight defined sites. Fronto-median impacts led to mostly bilateral and always multiple fractures in the posterior area of the bone, especially in the collum and the condyle. The fracture threshold was between 2.5 and 3.1 kN. Lateral impact caused fractures near the impact area as direct fractures of the ipsilateral corpus. Mainly single and double fractures were observed. For lateral impact the fracture threshold was between 0.6 and 0.8 kN.

Influence of age, gender, education and dexterity on upper limb motor performance in Parkinsonian patients and healthy controls.

Finger tapping, the most widely used test for evaluating motor dysfunction in Parkinson's disease (PD), was found to react sensitively to disease specific factors like disease severity and changes in medication. A possible interference caused by disease unrelated demographic factors--age, gender, education and dexterity--however has not yet been studied systematically. Various components of tapping performance of 187 healthy subjects and 200 PD patients were assessed by means of the BRAIN TEST, a digitalized test battery. The effects of demographic factors--above all education and age--were found to be significant. These influences generally affect different aspects of movement to a different extent, with speed and akinesia being affected more severely than dysmetria and arrhythmokinesis. Our study suggests that whenever precise assement of upper limb motor performance is needed, specific corrections for these demographic factors in both healthy controls and PD patients are necessary.

East-west differences in the organization of botulinum toxin use in nine Central European countries.

Availability and quality of expensive treatment modalities such as botulinum toxin (BTX) largely depend on organizational aspects such as costs, reimbursement by insurance companies, expertise and facilities for expert training, and the propagation of research. To investigate which determinants influence the organization of BTX' use throughout nine Central European countries (Austria, Croatia, Czech Republic, Germany, Hungary, Italy, Slovakia, Slovenia and Switzerland) we sent out questionnaires to leading BTX experts and consulted data banks of manufacturers and bulletins of international organizations. In Western European countries, there is a tendency for users to organize themselves in formal groups and to concentrate on research whereas the way how BTX is provided is diverse regarding qualifications of specialists and institutions. In the post-communist Eastern European countries, we found a tendency towards a centralized system of reimbursement and BTX treatment seems to be more in the hands of neurologists than any other specialists. Strong correlations were observed between the number of BTX centres, degree of organization of user groups and number of scientific publications, on the one hand, and parameters of healthcare performance and socioeconomic determinants, on the other. Our study suggests that in the nine countries surveyed, organizational aspects of BTX use vary considerably, whilst similarities are based mainly on socioeconomic rather than socio-demographic determinants.

Ascites fluid and plasma calprotectin concentrations in liver disease.

BACKGROUND: Calprotectin, a marker of neutrophil activation, has been associated with a poor prognosis in alcohol-induced cirrhosis. The aims were to study concentrations of calprotectin in patients with various liver diseases, and to further investigate the prognostic value of calprotectin in cirrhosis. METHODS: Plasma calprotectin concentrations were determined in 84 patients with alcohol-induced liver disease, 32 hepatitis B or C infected patients, 33 patients with liver disease of other aetiologies, 7 patients with combined aetiologies and in 24 patients with malignant disease. Thirty healthy individuals were included as controls. Ascites calprotectin concentrations were determined in patients with ascites (n = 75). Follow-up for survival was performed after a median observation period of 10 months. RESULTS: Increased plasma and ascites calprotectin concentrations were observed in malignant disease compared to non-malignant disease (P < 0.0001). Plasma calprotectin concentrations were low in viral liver disease compared to patients with non-viral liver disease (P = 0.02) and to controls (P = 0.0002). Plasma calprotectin (>median) was a highly significant marker of poor survival in alcohol-induced cirrhosis (P = 0.001), but was of no prognostic value in non-alcohol-induced cirrhosis (P = 0.88). In decompensated cirrhosis high (>upper quartile) ascites calprotectin concentrations were associated with an increased mortality (P = 0.002), as were high (>median) plasma calprotectin levels (P = 0.009). CONCLUSION: The prognostic importance of calprotectin in alcohol-induced cirrhosis is confirmed and demonstrated as specific for alcohol-induced liver disease. Low calprotectin levels are indicated in viral liver disease, and an association between high ascites calprotectin levels and malignant ascites was observed.

[Botulinum toxin--the dose controls the poison. A historical sketch]. / Botulinumtoxin--Die Dosis macht das Gift. Ein historischer Abriss.

Botulism, a potentially lethal form of paralytic food poisoning, was described as early as 1793. Basic research, especially in the late nineteenth and early twentieth centuries, revealed that botulism is caused by exotoxins. Further biochemical work around and after the Second World War gave insight into the molecular structure of seven different serotypes of botulinum toxin (BT/A-G) as well as into its acetylcholine blocking mode of action. In 1977, Scott treated patients with strabism by injecting minute amounts of purified BT/A. In short sequence, BT proved effective in blepharospasm, cervical dystonia, and various off-label indications. In the near future, registration of these new indications, marketing of new serotypes (BT/B), and availability of more practical antibody tests can be expected. The first applications of BT were performed by Roggenkaemper, Dressler, and Benecke in Germany and by Poewe and Auff in Austria. According to a worldwide trend, a rapid expansion regarding BT users and indications followed. Formation of BT competence centers in both countries aims at maintaining high standards in BT research and education.

Diagnosis and surgical management of intraspinal synovial cysts: report of 19 cases.

OBJECTIVE: Synovial cysts of the vertebral facet joints are a source of nerve root compression. Different surgical procedures are in use, but no consensus has been formed so far as to which method should be used in synovial cysts. To clarify the role of surgical management, the efficacy of operative procedures and factors influencing the outcome in our own series of 19 patients treated between 1994 and 1998 were analysed. METHODS: Nineteen patients with a mean age of 65 years underwent surgery for medically intractable radicular pain or neurological deficits caused by synovial cysts. The patients' records were retrospectively analysed for neurological deficits, cysts diameter, operative approach, segmental hypermobility, and clinical outcome; CT and MRI were analysed for additional degenerative changes. RESULTS: In 17 patients an excellent result and in two patients a good postoperative result was achieved. Twelve patients were found to have hypermobility of the facet joints and six had spondylolisthesis. There was no correlation between cyst diameter, operative approach, and outcome. No intraoperative or postoperative complications occurred. CONCLUSIONS: Age and hypermobility may play a part in the aetiology of facet joint synovial cysts. As all operative strategies showed equally good clinical outcome, total excision via a small flavectomy as the least invasive approach should be considered therapy of choice in patients with cysts causing neurological deficits.

The Bradykinesia Akinesia Incoordination Test (BRAIN TEST), an objective and user-friendly means to evaluate patients with parkinsonism.

The BRAIN TEST, a computerized alternating finger tapping test, was performed on 154 patients with parkinsonism to assess whether the test could be used as an objective tool to evaluate reliably the severity of Parkinson's disease (PD). Patients were instructed to tap two marked computer keyboard keys as fast and as accurately as possible for 60 seconds. The test generates the following variables: (1) kinesia score (KS)--number of keystrokes/min, (2) akinesia time (AT)--cumulative time that keys are depressed, (3) dysmetria score (DS)--a weighted score generated from incorrectly hit keys and corrected for speed, and (4) arrhythmia score (AS)--variance of the time interval between individual keystrokes. Among parkinsonian patients, we found a significant correlation between the four test parameters and PD rating scores of the Hoehn & Yahr, Schwab & England, and Unified PD Rating Scales (KS, AS, and AT p <0.001 and DS p <0.05). When compared with 73 parkinsonian patients 73 age- and sex-matched control subjects showed significantly higher KS and lower AT (p <0.001) as well as lower DS and AS (p = 0.05). The BRAIN TEST is a reliable and practical tool for evaluating the severity of parkinsonism and for distinguishing subjects with parkinsonism from normal control subjects. A version of the BRAIN TEST is available by FTP on the worldwide web (http://www.anaesthetist.com/software/brain.htm).

[Experimental and finite-element models for the assessment of mandibular deformation under mechanical loading]. / Experimentelle und Finite-Elemente-Analyse der Biomechanik des Unterkiefers unter Belastung.

Biomechanical investigations of the mandible are difficult to perform due to a variety of conditions involved. For the appropriate reconstruction of biomechanical properties, a geometrically correct body model has to be established which fits to complex in vivo conditions. The aim of our study was to evaluate the use of finite-element models (FEM) for the assessment of mandibular deformation under mechanical loading. Explanted human mandibles (n = 5) were investigated by strain gauges to determine the individual strain distribution under mechanical loading. FEM analysis based on a computed tomograph (CT) was performed and the results were matched with the test data. Our study demonstrates only minor interindividual differences in the strain distribution for each load studied. The mechanical response in terms of deformation was found to depend mainly on gross geometrical properties and to a minor extent on the various other variables. At all positions the maximum principal strain was tensile, the minimum principal strain was compressive, and the absolute strain values were correlated with the magnitude of the applied force. CT-based FEM analysis revealed the utility of mathematical models to approximate simulated data our experimental results. Hence, FEM analysis is a non-invasive tool in the prediction of biomechanical behaviour of individual mandibles and therefore may help in trauma reconstruction and treatment planning.

Neopterin and interleukin-8--prognosis in alcohol-induced cirrhosis.

BACKGROUND: Neutrophil cytotoxity and activated macrophages have been implicated in the pathogenesis of alcohol-induced liver disease. The aim of this study was to relate plasma levels of neopterin, a marker of activation of the cellular immune system, and IL-8, a neutrophil chemotactic factor, with severity of liver disease and prognosis in patients with alcohol-induced cirrhosis. METHODS: Plasma concentrations of neopterin and IL-8 were assessed in 81 patients with alcohol-induced cirrhosis admitted to the Department of Medicine B, Bispebjerg Hospital, Copenhagen, Denmark, and in 16 healthy controls. After a median follow-up period of 5 years, mortality and death causes were registered. The patients were divided into groups according to the major contributing cause of death: infection, upper gastrointestinal bleeding or hepatic coma. RESULTS: Neopterin and IL-8 levels were increased in the cirrhosis patients, but not significantly related to Child-Pugh classification. Five-year mortality was 67%. High neopterin levels (>upper quartile) were an independent predictor of death (p=0.01, Log rank and p<0.02, Cox). High IL-8 levels (>upper quartile) were of no significant prognostic value for overall mortality. Causes of death related mortality were as follows (Log rank): Neopterin; p=0.009, p=0.84 and p=0.94, and IL-8; p=0.36, p=0.002 and p=0.27, respectively, according to infection, bleeding and coma as causes of death. CONCLUSIONS: Neopterin and IL-8 plasma levels are raised in patients with alcohol-induced cirrhosis, and are predictive of mortality associated with infections and upper gastrointestinal bleeding, respectively.

Is IgM of diagnostic value in case of delayed intrathecal production of IgG antibodies?

The neurological manifestations of Lyme borreliosis comprise a wide range of clinical signs. However, these symptoms might have other aetiologies. Therefore detection of intrathecal production of specific antibodies is necessary to confirm the clinical assumption of neuroborreliosis (NB). In case of delayed intrathecal production of specific IgG antibodies, detection of IgM could play a role in the early diagnosis of NB. To clarify whether IgM is of diagnostic value in such cases, paired CSF serum samples from 176 patients with suspected NB admitted to the department of Neurology, Karl Franzens University, Graz, Austria, were tested. Testing was performed with the IDEA Neuroborreliosis Kit (Dako, Denmark) and Enzygnost Borreliosis (Behring, Germany) and results of both methods were compared. According to well defined criteria 63 of the 176 patients had defined NB and 113 were regarded as possible NB. Twelve out of 63 patients with defined NB had delayed intrathecal IgG production. Only one patient with delayed IgG production had an intrathecal IgM production prior to IgG. In all patients with possible NB no intrathecal production of IgM was detected. At the time of the first lumbar puncture IgG intrathecal production could be detected with the IDEA seven times more often than with the Enzygnost Borreliosis. The determination of intrathecal production of IgM does not appear to be of diagnostic value in patients with delayed IgG antibody production. Therefore a consecutive lumbar puncture is more likely to confirm clinical assumption if there is strong clinical evidence of NB.

Mannan binding lectin in rheumatoid arthritis. A longitudinal study.

OBJECTIVE: Low serum levels of mannan binding lectin (MBL) are associated with increased risk of recurrent infections. We determined whether there was an association between serum MBL levels and the course and prognosis of rheumatoid arthritis (RA). METHODS: MBL was analyzed in sera from 99 patients with RA who were included in a longterm prospective study. RESULTS: Compared with controls, a high fraction of patients lacked detectable MBL in serum (11 vs 3%; p = 0.025). Comparing patients with MBL serum levels above and below the median revealed that those with levels below the median were younger at onset of RA (p = 0.043) and had higher erythrocyte sedimentation rate (p = 0.006), joint swelling score (p = 0.019), limitation of joint motion score (p = 0.027), and annual increase in radiographic destruction score (p = 0.053). CONCLUSION: MBL insufficiency may be a contributing pathogenetic factor in RA.

[Intestinal tuberculosis]. / Intestinal tuberkulose.

Since the symptoms and clinical presentation of intestinal tuberculosis is nonspecific, the diagnosis is frequently delayed and may be achieved at autopsy only. Intestinal tuberculosis is very rare in Denmark, but may now be seen more often because of increasing numbers of immigrants from countries of the third world with a high prevalence of tuberculosis. A case of intestinal tuberculosis in a 28 year old Somalian female is reported. Methods of diagnosing intestinal tuberculosis are commented, and the frequent necessity of starting medical treatment before a bacteriological diagnosis is reached is emphasized.