Ptychographic reconstruction of attosecond pulses.

We demonstrate a new attosecond pulse reconstruction modality which uses an algorithm that is derived from ptychography. In contrast to other methods, energy and delay sampling are not correlated, and as a result, the number of electron spectra to record is considerably smaller. Together with the robust algorithm, this leads to a more precise and fast convergence of the reconstruction.

Ptychographic ultrafast pulse reconstruction.

We demonstrate a new ultrafast pulse reconstruction modality that is somewhat reminiscent of frequency-resolved optical gating but uses a modified setup and a conceptually different reconstruction algorithm that is derived from ptychography. Even though it is a second-order correlation scheme, it shows no time ambiguity. Moreover, the number of spectra to record is considerably smaller than in most other related schemes which, together with a robust algorithm, leads to extremely fast convergence of the reconstruction.

PCR examination of bronchoalveolar lavage samples is a useful tool in pre-clinical diagnosis of ovine pulmonary adenocarcinoma (Jaagsiekte).

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung tumour of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The disease is a particular problem in flocks in many parts of the world. The aim of the study was to assess screening methods for individual animals as a prelude to future eradication trials. Results of histological examination were used as the standard to evaluate the relative sensitivity and specificity of an established heminested polymerase chain reaction (PCR) test for JSRV proviral DNA from blood and bronchoalveolar lavage (BAL) samples. PCR results from tissue samples are included as control data. PCR testing of blood samples was found to have an estimated sensitivity of only 10% (95% confidence interval (CI) 3-20) while the sensitivity of the PCR test on BAL samples was 89% (CI 79-96) in comparison to the results of histological examination. We conclude that PCR testing of BAL samples is an effective confirmatory test for sheep with suspected clinical OPA. It is also a useful tool for the pre-clinical identification of individual infected sheep within an infected flock and therefore may prove beneficial in future control or eradication programmes.

Eradication of ovine pulmonary adenocarcinoma by motherless rearing of lambs.

The principles of maedi-visna eradication programmes were applied to a field trial for the eradication of ovine pulmonary adenocarcinoma (OPA). In two maternal flocks the prevalence of gross and histological lesions in slaughtered animals was 18.3 per cent and 29.8 per cent, respectively. The lambing period was supervised for three consecutive years from 1999 to 2001, during which the lambs were taken away from their mothers at birth, deprived of maternal colostrum, and hand-reared away from other sheep. Over the three-year period, 322 hand-reared animals, mainly male lambs between 10 and 14 months old, were slaughtered; their lungs were examined grossly, 52.5 per cent of them were examined histologically, and 105 samples of caudal mediastinal lymph nodes were examined by PCR. No OPA tumours were detected in the slaughter specimens from the derived flock, but one lamb had histological lesions in one lung location; intrauterine transmission was ruled out in this case. No clinical OPA has subsequently been observed in the hand-reared flock. Bronchoalveolar lavage samples from the breeding stock were examined by PCR in order to rule out further subclinical cases of OPA. No Jaagsiekte retrovirus was detected in any of the 488 samples.

Rapid Discovery of De Novo Deleterious Mutations in Cattle Enhances the Value of Livestock as Model Species.

In humans, the clinical and molecular characterization of sporadic syndromes is often hindered by the small number of patients and the difficulty in developing animal models for severe dominant conditions. Here we show that the availability of large data sets of whole-genome sequences, high-density SNP chip genotypes and extensive recording of phenotype offers an unprecedented opportunity to quickly dissect the genetic architecture of severe dominant conditions in livestock. We report on the identification of seven dominant de novo mutations in CHD7, COL1A1, COL2A1, COPA, and MITF and exploit the structure of cattle populations to describe their clinical consequences and map modifier loci. Moreover, we demonstrate that the emergence of recessive genetic defects can be monitored by detecting de novo deleterious mutations in the genome of bulls used for artificial insemination. These results demonstrate the attractiveness of cattle as a model species in the post genomic era, particularly to confirm the genetic aetiology of isolated clinical case reports in humans.

Facilitation of picture naming after repetitive transcranial magnetic stimulation.

OBJECTIVE: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on picture naming. BACKGROUND: Previous studies have shown that rTMS disrupts ongoing speech processes when delivered over frontal or parietal areas of the dominant hemisphere. METHODS: In 15 healthy right-handed male individuals, rTMS trains of 20 Hz with a duration of 2 seconds and an intensity of 55% of maximum stimulator output were delivered either to Wernicke's area, to the right-hemisphere homologue of Wernicke's area, to Broca's area, or to the primary visual cortex. Twenty black-and-white line drawings, which the individuals had to name as quickly as possible, were shown immediately after the completion of rTMS and again 2 minutes later. RESULTS: Immediately after the end of a train over Wernicke's area a shortening of naming latency was observed compared with naming without rTMS (p < 0.001). No significant effects on picture naming were observed 2 minutes later or at any time after stimulation of the right-hemisphere homologues of Wernicke's area, Broca's area, or the visual cortex. CONCLUSION: Repetitive transcranial magnetic stimulation over Wernicke's area leads to a brief facilitation of picture naming by shortening linguistic processing time.

Repetitive transcranial magnetic stimulation effects on language function depend on the stimulation parameters.

In previous studies it has been shown that picture-naming latencies can be facilitated with both suprathreshold single and repetitive transcranial magnetic stimulation (TMS/rTMS) over Wernicke's area. The aim of this study was to investigate whether low-frequency rTMS (1 Hz) or high-frequency rTMS (20 Hz) at subthreshold intensities is also capable of influencing picture naming. In 16 healthy right-hand male subjects, trains of 1 Hz or 20 Hz were applied over either Wernicke's area, Broca's area, or the primary visual cortex. The subjects had to name 20 black-and-white line drawings, which were shown immediately after rTMS and again 2 minutes later. Naming latency could be facilitated only immediately after Wernicke's area stimulation at a frequency of 20 Hz and at an intensity of 55% of the maximal stimulator output, which was more than the motor threshold. All other stimulation procedures failed to influence naming latencies. These results indicate that language functions can be facilitated in healthy subjects only by high-frequency rTMS with intensities at or above the motor threshold.

[Determinants of the global quality of life after polytrauma]. / Determinanten der globalen Lebensqualität nach Polytrauma.

This study investigated multiple trauma patients, who were injured between 1991 and 1995 and treated in our department. The aim of this study was to identify the determinants of quality of life after multiple trauma. From a total of 186 patients 173 (93%) were examined. The patients were asked to rate their quality of life according to the Nottingham Health Profile (NHP) and to a visual analogue scale (VAS). The VAS and the NHP isolated the age of the patients, the duration of artificial respiration, and the duration of rehabilitation as the predictors for a reduced overall quality of life. These results show that quality of life after multiple trauma not only depends on the severity of injury but also on demographic and psychosocial factors.

Corneal dermoid in a dwarf rabbit (Oryctolagus cuniculi).

Histology after superficial keratectomy verified our diagnosis of corneal dermoid in a dwarf rabbit (Oryctolagus cuniculi). To our knowledge, this lesion has not been reported previously to occur in dwarf rabbits. Ocular dermoids should be considered as a differential diagnosis for corneal abnormalities in the rabbit.

[Case report: Yersinia enterocolitica septicemia in an American minipig]. / Fallbericht: Yersinia enterocolitica-Septikämie bei einem American Minipig.

A natural, lethal enteritis and septicaemia caused by Yersinia enterocolitica in an American Minipig piglet is reported. The isolated strain was identified as serotype O:3 and biotype 4. Pathomorphological examination of the animal revealed a severe fibrinonecrotic ileitis and typhlocolitis. Pyogranulomatous lesions were detected in regional lymph nodes and several organs.

[Iscom (Immuno Stimulating Complex)-vaccine of equine influenza virus--transmission electron microscopic investigation and literature review]. / Iscom (Immuno Stimulating Complex)-Vakzine des equinen Influenza-Virus--transmissionselektronenmikroskopische Chargenüberwachung und Literaturübersicht.

Vaccines on the base of immunostimulating complexes are very rare in human and veterinary practice. Until now, Iscom vaccines mainly have been developed for scientific experimental investigations. Synthesis and preparation of Iscom vaccines, mainly basing on the reviewed literature, as well as electron microscopical investigations of Iscom structures and the monitoring of vaccine fractions of Iscoms are described. The equine influenza Iscom vaccine, developed by the Mallinckrodt Veterinary GmbH, is one of the first commercial Iscom vaccine used in veterinary medicine. In comparison with other commercially used vaccines, depending on the high level of antigen presentation of Iscom structures, a ten times higher antibody response is to be expected by the use of Iscom vaccines.

Porcine circovirus type 2-associated cerebellar vasculitis in postweaning multisystemic wasting syndrome (PMWS)-affected pigs.

Porcine circovirus type 2 (PCV2) is associated with several syndromes in growing pigs, including postweaning multisystemic wasting syndrome and porcine dermatitis and nephropathy syndrome. In the present study, a previously undescribed neurovascular disorder associated with a PCV2 infection is described. Sixteen pigs showed clinical signs of wasting and neurologic deficits. Acute hemorrhages and edema of cerebellar meninges and parenchyma due to a necrotizing vasculitis resulted in degeneration and necrosis of the gray and white matter. Few to numerous PCV2 DNA and antigen-bearing endothelial cells were detected in affected areas of the brain using in situ hybridization and immunohistochemistry. Conventional histochemical stains, as well as the detection of caspase 3 activity and DNA strand breaks by the terminal transferase dUTP nick end labeling assay, showed numerous apoptotic endothelial cells in the vascular lesions observed. Sequencing of various brain-derived PCV2-specific amplicons revealed a strong identity between different isolates and an 89 to 100% identity to previous isolates. The phylogenetic tree showed that there was no clustering of isolates correlating to clinical signs or geographic distribution. This previously undescribed PCV2-associated neurologic disease has features of both postweaning multisystemic wasting syndrome and, to a lesser extent, porcine dermatitis and nephropathy syndrome. The available evidence suggests that direct virus-induced apoptosis of endothelial cells plays a role in the pathogenesis of this unusual PCV2-associated cerebellar vasculitis.

Immunohistochemical studies in equine recurrent uveitis (ERU).

Despite extensive clinical research, the etiology of equine recurrent uveitis (ERU) is still unknown. After an immunologic pathogenesis was established in recurrent uveitis in humans, a similar pathogenic mechanism was assumed to exist in ERU. To investigate whether immunopathologic mechanisms are involved in ERU, 20 eyes of 15 horses with ERU were examined immunohistochemically with a T cell marker, B cell marker, and anti-major histocompatibility complex (MHC) class II antibodies. Twenty-six eyes of 20 horses were used for investigation of MHC class II antigen expression in normal equine eyes. In 18 eyes of 14 horses, the number of T cells in the inflammatory cell population within the uvea was assessed. In 16/18 eyes (89%), the T lymphocyte fraction was > 70%. This cell population was distributed mostly in a diffuse manner throughout the uvea and also within the mantle zone of follicular lymphocytic aggregates. Foci of B lymphocytes could be found within the center of follicular aggregates in three eyes. The expression of MHC class II antigen on resident ocular cells was evaluated in 10 eyes of six horses with ERU. An increase of MHC class II antigen expression in the trabecular meshwork and on the nonpigmented ciliary epithelium was noted as was a deviant expression on proliferating Müller cells and retinal pigment epithelial cells. The predominance of T cells in the inflammatory infiltrates supports the central role of a cell-mediated immune response. Furthermore, the observation of a deviant MHC class II expression on resident ocular cells suggests that aberrant immune regulation may play a role in the pathogenesis of ERU.

Osteogenesis imperfecta in two litters of dachshunds.

A clinical, morphologic, ultrastructural, and genetic study was performed on five rough-coated dachshund semisiblings with osteogenesis imperfecta (OI). Clinical signs consisted of pain, spontaneous bone and teeth fractures, joint hyperlaxity, and reduced bone density on radiography. Primary teeth were extremely thin-walled and brittle. The hallmark of the disease was a severe osteopenia characterized by impairment of lamellar bone formation in the long bones, skull, and vertebral column. No deformity or dwarfism was present. The columns of chondrocytes and primary trabeculae in the epiphyses and metaphyses were histologically normal. An abrupt failure of secondary spongiosa and lamellar bone formation was evident in the medullary and cortical zones in all animals. The few existing trabeculae consisted of woven bone. There was no increase in the number and size of osteoclasts or lacunae. In the teeth, the dentine layers were thin and lacked a tubular pattern. Ultrastructurally, osteoid apposition on bone surfaces was reduced, and small numbers of large cytoplasmic vacuoles were present in a few osteoblasts. Molecular analyses of the collagen type I-encoding genes COL1A1 and COL1A2 revealed several nucleotide differences compared with the published canine sequences but were not significant for OI. Therefore, OI in these Dachshund litters was characterized by a severe, generalized osteopenia and dentinopenia. This pattern of reduced bone formation is suggestive of defective production of collagen type I.

Facilitation of picture naming by focal transcranial magnetic stimulation of Wernicke's area.

On the basis of an evolutionary concept of language it was postulated that activation of the motor systems for arm movements, which are phylogenetically older, should facilitate language processes. In aphasic subjects picture naming can be improved by a concomitant movement of the dominant arm. In the present study it was investigated whether a similar facilitation can be observed in normal subjects by studying the effects of transcranial magnetic stimulation (TMS) on picture naming latencies. Suprathreshold focal TMS was applied to the left motor cortex for proximal arm muscles in right-handed subjects. The effects were compared with TMS of Wernicke's area. While TMS of the motor cortex and the non-dominant temporal lobe had no facilitatory effects, TMS of Wernicke's area decreased picture naming latencies significantly when TMS preceded picture presentation by 500 or 1000 ms. The observed effects depended on the intensity of the stimulus used. While clearly present with intensities of 35% and 55% of maximum output the facilitation disappeared with higher stimulation intensities. It is concluded that focal magnetic stimulation is able to facilitate lexical processes due to a general preactivation of language-related neuronal networks when delivered over Wernicke's area.

Renal coccidiosis with cystic tubular dilatation in four bats.

Renal coccidiosis was diagnosed in four bats of different species (Pipistrellus pipistrellus, Myotis mystacinus, M. nattereri, and Nyctalus noctula). Multiple white and partly indented foci up to 2 mm in diameter were visible on the renal surface. Histologically, the foci appeared as cystic dilated tubules with proliferated epithelium. Asexual and sexual coccidian stages were seen in the epithelial cells, and the extremely distended tubular lumina were filled with schizonts, free zoites, microgamonts, macrogamonts, and unsporulated oocysts. Because the majority of the renal tissue appeared uninvolved in the disease process at the gross and histologic levels and there was no evidence for uremia in other organs, renal function was probably not impaired. Precise classification of the coccidia was impossible because no sporulated oocysts were available. The parasite morphology and the hitherto unreported cystic dilatation of infected tubules containing all developmental stages differ from renal coccidioses reported previously and therefore suggest an undescribed coccidian species.

Generalized AA-amyloidosis in Siberian tigers (Panthera tigris altaica) with predominant renal medullary amyloid deposition.

Generalized amyloidosis with predominant renal medullary amyloid deposition was found in four closely related Siberian tigers (Panthera tigris altaica) suffering from end stage kidney diseases. Only minimal to mild amounts of amyloid were deposited in various organs outside the kidneys with individually variable organ involvement. The Congo red staining affinity of amyloid deposits was sensitive to potassium permanganate oxidation. The deposits were further characterized as being of the amyloid-A (AA) type by immunohistochemistry using the mouse monoclonal antibody mc4 directed against a conserved region of the human AA-protein. A combination of immunohistochemistry and Congo red staining was much more sensitive for the diagnosis of amyloid deposits than Congo red staining alone. With this combination, even minimal amyloid deposits were detected that had been missed in the first reading using Congo-red-stained slides alone. Since no common primary cause was identified, the amyloidosis was classified as idiopathic generalized AA-amyloidosis with a potential familial predisposition.

[Neuropsychological effects of preventive CNS irradiation in adult tumor patients]. / Neuropsychologische Effekte der prophylaktischen ZNS-Bestrahlung bei erwachsenen Tumorpatienten.

Prophylactic cranial irradiation (PCI) has led to marked prolongation of survival, but also to intellectual and neuropsychological retardation in children with ALL. PCI has also been conducted in adult patients with small-cell bronchial carcinoma in the stage of minimal disease or with breast cancer. There are no studies assessing cognitive or other neuropsychological consequences of PCI in adult cancer patients. We report on a longitudinal prospective study of the effects of PCI on five major neuropsychological domains (intelligence, concentration, attention, memory and psychomotor performance). We report on our ongoing study, in which up to now 11 patients with small-cell lung cancer undergoing PCI have been investigated. Patients are assessed immediately before therapy started as well as 4 weeks and 3 months after onset of PCI. The used instruments are Standard Progressive Matrices (SPM), d2 Concentration Test, Minimental State, Verbal Learning Test and Psychomotor Tests (Steadiness, Aiming, Tapping, Tracking, Pursuit Rotor Test). Although our sample is small, results indicate that there is no evidence for a decrease in neuropsychological abilities in adults after three months. This is in contrast to the observed results after PCI in children. As compared to baseline measures, differences in memory, intelligence, concentration and attention were marginal over time. Moreover the progress of motor performance skills showed no clear tendency.

A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal-results 6-18 months after implantation into New Zealand white rabbits.

OBJECTIVE: To determine whether corrodible materials may be safely used as biodegradable cardiovascular implants. DESIGN: Corrodible iron stents (> 99.8% iron) were produced from pure iron and laser cut with a stent design similar to a commercially available permanent stent (PUVA-AS16). A total of 16 NOR-I stents were implanted into the native descending aorta of 16 New Zealand white rabbits (mean luminal diameter at the implantation site 3.4 mm, balloon diameter to vessel diameter ratio 1.13). RESULTS: No thromboembolic complications and no adverse events occurred during the follow up of 6-18 months. All stents were patent at repeat angiography after 6 (n = 9), 12 (n = 5), and 18 months (n = 2) with no significant neointimal proliferation, no pronounced inflammatory response, and no systemic toxicity. CONCLUSIONS: This initial in vivo experience suggests that degradable iron stents can be safely implanted without significant obstruction of the stented vessel caused by inflammation, neointimal proliferation, or thrombotic events.

Prognosis of salivary adenocarcinomas. A retrospective study of 52 cases with special regard to cytochemically assessed nuclear DNA content.

52 salivary adenocarcinomas of the years 1965-1980 from the files of the Salivary Gland Registry, Institute of Pathology, University of Hamburg, were evaluated retrospectively with regard to clinical follow up and cytochemically assessed nuclear DNA content. The age distribution showed a peak from the 6th to 8th decade (range 3 to 87 years). The m:f ratio was 1:1.36, the mean age was 59.3 years. Over 80% of the tumours were located in the major salivary glands. The clinical course was characterized by metastases present at initial diagnosis (16 cases), subsequent development of metastases (9 cases), local recurrence (15 cases) or death from tumour (10 cases) and was related to differentiation, grade 3 tumours showing the worse clinical courses. In 37 cases, nuclear DNA content was determined by a single scanning cytophotometry device. 28 cases were diploid, 9 were atypical. The clinical course was significantly related to the histogram type, atypical tumours showing a dismal prognosis.