A combined active shape and mean appearance model for the reconstruction of segmental bone loss.

This study investigates the novel combination of an active shape and mean appearance model to estimate missing bone geometry and density distribution from sparse inputs simulating segmental bone loss of the femoral diaphysis. An active shape Gaussian Process Morphable model was trained on healthy right femurs of South African males to model shape. The density distribution was approximated based on the mean appearance of computed tomography images from the training set. Estimations of diaphyseal resections were obtained by probabilistic fitting of the active shape model to sparse inputs consisting of proximal and distal femoral data on computed tomography images. The resulting shape estimates of the diaphyseal resections were then used to map the mean appearance model to the patients' missing bone geometry, constructing density estimations. In this way, resected bone surfaces were estimated with an average error of 2.24 (0.5) mm. Density distributions were approximated within 87 (0.7) % of the intensity of the original target images before the simulated segmental bone loss. These results fall within the acceptable tolerances required for surgical planning and reconstruction of long bone defects.

Basal freeze-on generates complex ice-sheet stratigraphy.

Large, plume-like internal ice-layer-structures have been observed in radar images from both Antarctica and Greenland, rising from the ice-sheet base to up to half of the ice thickness. Their origins are not yet understood. Here, we simulate their genesis by basal freeze-on using numerical ice-flow modelling and analyse the transient evolution of the emerging ice-plume and the surrounding ice-layer structure as a function of both freeze-on rate and ice flux. We find good agreement between radar observations, modelled ice-plume geometry and internal layer structure, and further show that plume height relates primarily to ice-flux and only secondarily to freeze-on. An in-depth analysis, performed for Northern Greenland of observed spatial plume distribution related to ice flow, basal topography and water availability supports our findings regarding ice flux and suggests freeze-on is controlled by ascending subglacial water flow. Our results imply that widespread basal freeze-on strongly affects ice stratigraphy and consequently ice-core interpretations.

Detection efficiency of microchannel plates for e(-) and π(-) in the momentum range from 17.5 to 345 MeV/c.

High-energy e(-) and π(-) were measured by the multichannel plate (MCP) detector at the PiM1 beam line of the High Intensity Proton Accelerator Facilities located at the Paul Scherrer Institute, Villigen, Switzerland. The measurements provide the absolute detection efficiencies for these particles: 5.8% ± 0.5% for electrons in the beam momenta range 17.5-300 MeV/c and 6.0% ± 1.3% for pions in the beam momenta range 172-345 MeV/c. The pulse height distribution determined from the measurements is close to an exponential function with negative exponent, indicating that the particles penetrated the MCP material before producing the signal somewhere inside the channel. Low charge extraction and nominal gains of the MCP detector observed in this study are consistent with the proposed mechanism of the signal formation by penetrating radiation. A very similar MCP ion detector will be used in the Neutral Ion Mass (NIM) spectrometer designed for the JUICE mission of European Space Agency (ESA) to the Jupiter system, to perform measurements of the chemical composition of the Galilean moon exospheres. The detection efficiency for penetrating radiation determined in the present studies is important for the optimisation of the radiation shielding of the NIM detector against the high-rate and high-energy electrons trapped in Jupiter's magnetic field. Furthermore, the current studies indicate that MCP detectors can be useful to measure high-energy particle beams at high temporal resolution.

Processing-dependent and -independent pathways for recognition of iodinated contrast media by specific human T cells.

BACKGROUND: One to three percent of patients exposed to intravenously injected iodinated contrast media (CM) develop delayed hypersensitivity reactions. Positive patch test reactions, immunohistological findings, and CM-specific proliferation of T cells in vitro suggest a pathogenetic role for T cells. We have previously demonstrated that CM-specific T cell clones (TCCs) show a broad range of cross-reactivity to different CM. However, the mechanism of specific CM recognition by T cell receptors (TCRs) has not been analysed so far. OBJECTIVE: To determine how T cells specifically recognize CM. METHODS: CM-specific TCCs were generated from human blood of three CM-allergic patients and a specific TCR was transfected into a mouse T cell hybridoma. Functional analysis such as proliferation assays, IL-2 secretion assays, and calcium influx experiments were performed using irradiated, glutaraldehyde-fixed, CM-pre-incubated, human leucocyte antigen (HLA)-DR-matched or -mismatched antigen-presenting cells (APCs), and HLA-blocking antibodies. RESULTS: We identified two mechanisms of T cell stimulation: some TCCs and the transfectant reacted to CM independent of uptake by APCs because proliferation/IL-2 secretion occurred in the presence of glutaraldehyde-fixed APCs, and intracellular calcium increased within seconds after drug addition. Other TCCs required functional APCs, compatible with uptake and presentation of CM on MHC-class II molecules, as implied by three findings: (1) glutaraldehyde fixation of APCs abrogated presentation; (2) CM could not be washed away from CM-pre-incubated APCs; and (3) the optimal pulsing time was 10-20 h. Because allogeneic, MHC-matched, CM-pulsed APCs could induce proliferative responses as well, the ability of CM uptake and presentation is not unique to APCs from patients with CM-induced delayed hypersensitivity. CONCLUSION: Our data suggest that CM may be stimulatory for T cells either by direct binding to the MHC-TCR complex or by binding after uptake and processing by APCs. This questions the assumed inert nature of CM.

Time course of blood oxygenation level-dependent signal response after theta burst transcranial magnetic stimulation of the frontal eye field.

The aim of the current study was to examine the effect of theta burst repetitive transcranial magnetic stimulation (rTMS) on the blood oxygenation level-dependent (BOLD) activation during repeated functional magnetic resonance imaging (fMRI) measurements. Theta burst rTMS was applied over the right frontal eye field in seven healthy subjects. Subsequently, repeated fMRI measurements were performed during a saccade-fixation task (block design) 5, 20, 35, and 60 min after stimulation. We found that theta burst rTMS induced a strong and long-lasting decrease of the BOLD signal response of the stimulated frontal eye field at 20 and 35 min. Furthermore, less pronounced alterations of the BOLD signal response with different dynamics were found for remote oculomotor areas such as the left frontal eye field, the pre-supplementary eye field, the supplementary eye field, and both parietal eye fields. Recovery of the BOLD signal changes in the anterior remote areas started earlier than in the posterior remote areas. These results show that a) the major inhibitory impact of theta burst rTMS occurs directly in the stimulated area itself, and that b) a lower effect on remote, oculomotor areas can be induced.

Expression of intracellular calcium channels and pumps after partial hepatectomy in rat.

Ca(2+) signals regulate many cellular functions, including proliferation. They are governed by the inositol 1,4,5-trisphosphate receptor (IP(3)R), the only intracellular hepatic Ca(2+) channel and by the endoplasmic reticulum Ca(2+) pumps, SERCA. To characterise their role in regeneration, expression of their isoforms was studied after 2/3 hepatectomy by real-time quantitative PCR, Western blot and binding studies. We found an early increase in the expression of the IP(3)R isoform 1 which contrasted with the decrease of the expression of the IP(3)R isoforms 2 and 3 and of SERCA3. This results in a transient switch between IP(3)R isoforms 1 and 2, IP(3)R isoform 1 becoming predominant before the first round of mitosis. Binding studies detected a 30% diminution of the IP(3)R population at 24 h. In conclusion, the Ca(2+) signalling machinery is regulated, after hepatectomy, by changes in expression of the IP(3)R and SERCA isoforms to adapt Ca(2+) signals to the regenerative state.

Epidermal growth factor is decreased in liver of rats with biliary cirrhosis but does not act as paracrine growth factor immediately after hepatectomy.

BACKGROUND/AIMS: Epidermal growth factor, a potent mitogen for hepatocytes and cholangiocytes, is thought to act as an immediate-early gene after partial hepatectomy. Since regeneration is impaired in cirrhosis, we explored the expression of epidermal growth factor in cirrhotic rat liver immediately after partial hepatectomy. METHODS: Cirrhosis was induced by bile duct ligation (n=21); sham-operated animals served as controls (n=21). Twenty-five days after initial surgery animals were subjected to 70% partial hepatectomy or sham operation; the liver was sampled before surgery and 20, 40 and 90 min thereafter. Epidermal growth factor mRNA levels were assessed by quantitative reverse transcription polymerase chain reaction. Protein expression was estimated by immunohistochemistry using a polyclonal antibody against epidermal growth factor. RESULTS: Before hepatectomy, epidermal growth factor mRNA averaged 70.3+/-39.9 pg/microg of total RNA in controls; this was markedly decreased to 21.9+/-12.7 pg/microg RNA in bile duct ligation (p<0.01). Epidermal growth factor mRNA did not increase after partial hepatectomy in either group, with the exception of sham-operated controls. Immunohistochemistry revealed that partial hepatectomy had no effect on epidermal growth factor expression. Hepatocytes showed uniformly cytosolic epidermal growth factor in controls, while in bile duct ligation immunostaining was faint or absent. Cholangiocytes exhibited a strong cytosolic staining in all experimental groups. CONCLUSIONS: The present study shows that epidermal growth factor is reduced in the cirrhotic liver. This could contribute to the loss of parenchymal liver tissue observed in cirrhosis. The lack of up-regulation after PH sheds doubt on the role of epidermal growth factor as an immediate-early gene in hepatic regeneration. Further, we demonstrate that epidermal growth factor accumulates in cholangiocytes. This observation is strong evidence for involvement of the mitogen epidermal growth factor in the proliferation of bile ducts during cirrhogenesis.

[Prognostic factors and results after surgical treatment of idiopathic macular holes, stage 2 and 3]. / Prognostische Faktoren und Resultate nach operativer Behandlung idiopathischer Macula foramina Stadium 2 und 3.

PURPOSE: To determine prognostic factors, functional outcome and subjective rating after surgery for macular holes stage 2 and 3. METHODS: We studied 53 eyes of 49 patients undergoing vitreous surgery for macular holes stage 2 (46%) and 3 (54%). Mean follow-op was 114 weeks (32-204, std.dev. +/- 48), mean age 68.9 years (44-89, std.dev. +/- 6.8). 72% were female, 11% were pseudophakic, 19% phakic, 70% had a combined procedure (pars plana vitrectomy, phacoemulsification and IOL). Surgery consisted in a pars plana vitrectomy, peeling of epiretinal membranes and ILM, internal tamponade with SF6 (98%) resp. Si-oil in one case. Patients had to keep face-down position 6 x 20 minutes per day. RESULTS: The hole was completely closed in 90.6%. Anatomical failures included, 86% had an increase of VA, 41% = 5 lines (Final VA median 20/30, max. 20/20). No further increase of the retinal function occurred after 6 months. The visual result did not correlate with the duration of symptoms. 84% were satisfied with the outcome, subjective rating was not correlated with final VA or change of VA. 19% showed postoperative typical peripheral visual field defects. Visual field loss was not correlated with perioperative IOP elevation. CONCLUSION: Macular hole surgery has a high functional success rate. Postoperative visual field defects are an important problem.

[Vertical diplopia after cataract operation]. / Vertikale Diplopie nach Kataraktoperationen.

PURPOSE: Presentation and analysis of patients with vertical diplopia appearing after cataract surgery in retrobulbar anesthesia. SUBJECTS AND METHODS: Between 1990 and 1998 9 Patients with vertical diplopia following cataract surgery in retrobulbar anesthesia were studied in our Orthoptic Department. Each patient had complete orthoptic examination with Hess-screen-test. Additionally, some patients underwent neuroradiologic imaging and forced-duction testing. RESULTS: We subdivided the patients in a group of 4 patients with hypertropia and of 5 patients with hypotropia of the operated eye. All hypotropias were left-sided. Seven patients showed an overaction of the involved muscle without regression. Seven patients underwent surgery of a vertical muscle. Only 1 patient needed prismatic therapy postoperatively. The other 2 non-operated patients were satisfied with prisms alone. CONCLUSIONS: The proposed pathogenesis of vertical diplopia in these cases is fibrosis and contracture of the injured muscle, which could be due to anesthetic myotoxicity after direct injection into the muscle or to an intramuscular hemorrhage. On the other hand hypertropia could be a result of placement of bridle sutures. We discuss prevention and therapy of such complications.

Cloning of the rat ADAMTS-1 gene and its down regulation in endothelial cells in cirrhotic rats.

AIMS: This study was undertaken in order to identify genes which are regulated during the process of liver fibrosis. METHODS: The differential display method and RNA from rat endothelial cells before and after induction of cirrhosis were used. RESULTS: A 496 bp fragment, which was down regulated in liver endothelial cells from a cirrhotic animal, was cloned. The cloned fragment showed a 95% homology with the newly cloned mouse ADAMTS-1 gene (a disintegrin and metalloproteinase with thrombospondin motifs), which is implicated in inflammation. The fragment was found to span the 3' of exon 6, the whole exon 7 and the 5' of exon 8. Sequencing of the entire coding region of the rat gene showed a 94% homology at the nucleic acid level and 96% homology at the amino acid level. The sequences responsible for the function of the protein were conserved. Northern blot analysis, using the cloned fragment as a probe, confirmed the finding that the gene was down-regulated in endothelial cells derived from livers of cirrhotic animals. In situ PCR analysis localised the ADAMTS-1 gene in the liver endothelial cells from normal animals. CONCLUSIONS: Regulation of the expression of genes which belong to the metalloproteinase family in liver endothelial cells might be important in the development of liver cirrhosis.

Expression of inositol 1,4,5-trisphosphate receptor isoforms in rat cirrhosis.

Ca(2+) signals mediate the hepatic effects of numerous hormones and growth factors. Hepatic Ca(2+) signals are elicited by the inositol trisphosphate receptor, an intracellular Ca(2+) channel. Three isoforms of this receptor have been identified; they are expressed and regulated differently. We investigated the effect of liver fibrosis and cirrhosis on the hepatic expression of the inositol trisphosphate receptor isoforms. Two different rat models were used: bile duct ligation (fibrosis) and chronic exposure to CCl(4)/phenobarbital (cirrhosis). Messenger RNA levels were determined by ribonuclease protection assay (RPA), competitive polymerase chain reaction (PCR) followed by Southern blotting, and real-time quantitative PCR. Protein expression was assessed by Western blotting; tissue distribution was assessed by immunohistology. In control animals, isoform 2 was the predominant isoform, isoform 1 represented less than one third, and isoform 3 less than 1%. After bile duct ligation, expression of types 1 and 3 increased 1.9- and 5.7-fold, and expression of type 2 decreased 2. 5-fold at the protein level. After exposure to CCl(4)/phenobarbital, expression of types 1, 2, and 3 were 2.4-, 0.9-, and 4.2-fold their expression in control animals. Type 2 was localized to the apical domain of hepatocytes, consistent with a role for Ca(2+) signals in canalicular function. Type 3 was detectable in intrahepatic bile duct epithelial cells and not in hepatocytes, suggesting that Ca(2+) signals may be regulated differently in these cells. Signaling through inositol trisphosphate receptor participates in the pathogenesis of cirrhosis, because this process affects the expression of its isoforms.

[Diplopia after retrobulbar anesthesia in cataract surgery--a case report]. / Diplopie nach Retrobulbäranästhesie bei Kataraktoperation--ein Fallbericht.

A case report. A homolateral hypertrophia accompanied by diplopia occurred after retrobulbar anesthesia for cataract operation. In the course of the next few months a hypotrophia developed in the same eye. Two and a half years later a 5 mm recession of the inferior rectus muscle of the hypotrophic eye was performed under local anesthesia. The passive motility upwards improved already during the operation when the muscle was sectioned. After the operation there was a remarkable improvement of motility and field of vision. Conclusion. The cause of this diplopia is probably an injury of the inferior rectus muscle with a secondary contraction caused by the retrobulbar anesthesia. An injection along the inferior rectus muscle to achieve the retrobulbar anesthesia should be avoided.

[The accuracy of intravenous digital subtraction angiography regarding kidney arteries in hypertensive patients. A contribution to cost control in diagnostic medicine]. / Zur Treffsicherheit der intravenösen digitalen Subtraktionsangiographie bezüglich Nierenarterien bei Hypertonikern. Ein Beitrag zur Kostensenkung in der diagnostischen Medizin.

In a retrospective study the results of intravenous digital subtraction angiography (DSA) of renal arteries from 149 hypertensive outpatients investigated 1984 to 1989 at the University of Berne were evaluated. 118 i.v. DSA's (79%) were normal, 10 (7%) were inconclusive and 21 (14%) revealed stenosis. In 16 patients the course of the vessel and the degree of stenosis were verified by intraarterial DSA. In nine patients (6%) a significant stenosis was confirmed and subsequently treated by percutaneous transluminal angioplasty. Renal size was not a predictive parameter for stenosis in this population. Accessory renal arteries were found in 44% of patients with stenosis and only in 18% of those without. The late phase images of i.v. DSA revealed many morphologic abnormalities. The indication for i.v. DSA was assessed according to internationally accepted criteria: 1. severe hypertension, 2. hypertension refractory to treatment, 3. hypertension of sudden onset or aggravation, 4. onset of hypertension in patients younger than 20 or older than 50 years. In the group without stenosis (n = 118) 52 patients (44%) did not fulfill a single one of these criteria, whereas the patients with stenosis (n = 9) had at least one criterion fulfilled. Hypertensive patients should, therefore, only be studied by i.v. DSA if at least one criterion applies. 22,000 SFr. could thus have been saved without loss of medical quality and the treatment options.

[Pseudophakia--correction of unilateral cataract following penetrating eye injuries in children]. / Zur Pseudophakie--Korrektur der einseitigen Katarakt nach Bulbus eröffnenden Verletzungen bei Kindern.

Between 1972 and 1980 extracapsular cataract surgery was performed in 24 children, followed by implantation of an iris clip lens, after primary reconstruction of the anterior segment. Regular follow-ups were carried out at 3-month intervals. Discission of a secondary cataract was necessary in 19 cases. Visual acuity of 0.5 or more was achieved by 19 children. An orthophoria or exophoria was also found in 19 children with positive depth perception after a minimum of 2 and a maximum of 9.5 years' observation.

A puzzling triad: anorexia nervosa, high sweat electrolytes and indication to partial exocrine pancreatic insufficiency.

This report describes a 15-year-old girl with anorexia nervosa whose sweat electrolytes and pancreatic exocrine function were abnormal during a state of malnutrition. Both findings normalized when nutrition improved. The patient did not have any evidence of disorders known to be associated with an abnormal sweat test, including most importantly cystic fibrosis. It is postulated that the elevated sweat electrolytes and the pancreatic insufficiency developed in this patient secondary to malnutrition. The pathophysiological mechanism for both phenomena remains obscure. It is recommended that positive sweat tests in malnourished children should be repeated several times in a corrected nutritional state in order to obviate an erroneous diagnosis of cystic fibrosis.