Detection of early infarction signs with machine learning-based diagnosis by means of the Alberta Stroke Program Early CT score (ASPECTS) in the clinical routine.

PURPOSE: New software solutions emerged to support radiologists in image interpretation in acute ischemic stroke. This study aimed to validate the performance of computer-aided assessment of the Alberta Stroke Program Early CT score (ASPECTS) for detecting signs of early infarction. METHODS: ASPECT scores were assessed in 119 CT scans of patients with acute middle cerebral artery ischemia. Patient collective was differentiated according to (I) normal brain, (II) leukoencephalopathic changes, (III) infarcts, and (IV) atypical parenchymal defects (multiple sclerosis, etc.). ASPECTS assessments were automatically provided by the software package e-ASPECTS (Brainomix®, UK) (A). Subsequently, three neuroradiologists (B), (C), and (D) examined independently 2380 brain regions. Interrater comparison was performed with the definite infarct core as reference standard after best medical care (thrombolysis and/or thrombectomy). RESULTS: Interrater comparison revealed higher correlation coefficient of (B) 0.71, (C) 0.76, and of (D) 0.80 with definite infarct core compared to (A) 0.59 for ASPECTS assessment in the acute ischemic stroke setting. While (B), (C), and (D) showed a significant correlation for individual patient groups (I), (II), (III), and (IV), except for (D) (II), (A) was not significant in patient groups with pre-existing changes (II), (III), and (IV). The following sensitivities, specificities, PPV, NPV, and accuracies given in percent were achieved: (A) 83, 57, 55, 82, and 67; (B) 74, 76, 69, 83, and 77; (C) 80.8, 85.2, 76, 84, and 80; (D) 63, 90.7, 82, 79, and 80, respectively. CONCLUSION: For ASPECTS assessment, the examined software may provide valid data in case of normal brain. It may enhance the work of neuroradiologists in clinical decision making. A final human check for plausibility is needed, particularly in patient groups with pre-existing cerebral changes.

Comparison of eye-lens doses imparted during interventional and non-interventional neuroimaging techniques for assessment of intracranial aneurysms.

BACKGROUND: A neurointerventional examination of intracranial aneurysms often involves the eye lens in the primary beam of radiation. OBJECTIVE: To assess and compare eye-lens doses imparted during interventional and non-interventional imaging techniques for the examination of intracranial aneurysms. METHODS: We performed a phantom study on an anthropomorphic phantom (ATOM dosimetry phantom 702-D; CIRS, Norfolk, Virginia, USA) and assessed eye-lens doses with thermoluminescent dosimeters (TLDs) type 100 (LiF:Mg, Ti) during (1) interventional (depiction of all cerebral arteries with triple 3D-rotational angiography and twice 2-plane DSA anteroposterior and lateral projections) and (2) non-interventional (CT angiography (CTA)) diagnosis of intracranial aneurysms. Eye-lens doses were calculated following recommendations of the ICRP 103. Image quality was analysed in retrospective by two experienced radiologists on the basis of non-interventional and interventional pan-angiography examinations of patients with incidental aneurysms (n=50) on a five-point Likert scale. RESULTS: The following eye-lens doses were assessed: (1) interventional setting (triple 3D-rotational angiography and twice 2-plane DSA anteroposterior and lateral projections) 12 mGy; (2) non-interventional setting (CTA) 4.1 mGy. Image quality for depiction of intracranial aneurysms (>3 mm) was evaluated as good by both readers for both imaging techniques. CONCLUSIONS: Eye-lens doses are markedly higher during the interventional than during the non-interventional diagnosis of intracranial aneurysms. For the eye-lens dose, CTA offers considerable radiation dose savings in the diagnosis of intracranial aneurysms.

Comparison of radiation doses imparted during 128-, 256-, 384-multislice CT-scanners and cone beam computed tomography for intra- and perioperative cochlear implant assessment.

PURPOSE: To examine radiation-doses imparted during multislice (MSCT) and cone-beam computed-tomography (CBCT) for perioperative examination of cochlear-implant insertion. METHODS: Radiation-doses were assessed during standardized petrous-bone CT-protocols at different MSCT ((I) single-source CT-scanner Somatom-Definition-AS+, (II) 2nd generation of dual-source CT-scanner Somatom-Definition-Flash, (III) 3rd generation of dual-source CT-scanner Somatom-Force and at the CBCT Ziehm-Vision-RFD3D ((IV) (a) RFD-3D (Standard-modifier), (b) RFD-3D (Low-dose-modifier)). Image quality was examined by two radiologists appraising electrode-array placement, quality-control of cochlear-implant surgery and complications based on real patients' examinations (n=78). RESULTS: In MSCT-setting following radiation-doses were assessed (CTDIw; DLP): (I) 21.5mGy; 216mGycm; (II) 19.7mGy; 195mGycm; (III) 12.7mGy; 127mGycm; in the CBCT setting radiation doses were distributed as follows: (IV) (a) 1.9mGy; 19.4mGycm; (b) 1.2mGy; 12.9mGycm. Overall, image quality was evaluated as good for both, MSCT- and CBCT-examinations, with a good interrater reliability (r=0.81). CONCLUSION: CBCT bears considerable dose-saving potential for the perioperative examination of cochlear-implant insertion while maintaining adequate image quality.

Dose comparison of classical 2-plane DSA and 3D rotational angiography for the assessment of intracranial aneurysms.

INTRODUCTION: The purpose of this experimental phantom study was to compare radiation doses imparted to patients undergoing classical two-plane digital subtraction angiography (2-plane DSA) and 3D rotational angiography in interventional neuroradiology. METHODS: Thermoluminescence dosimeter (TLD) measurements were performed at an anthropomorphic phantom using a digital interventional angiography system. Two-plane DSA included posterior/anterior (PA) and lateral (LAT) projections (frame-rate, 7.6 frames (PA) and 9.8 frames (LAT) for a scan time of approximately 8 s; image intensifier 27 cm (PA) and 25 cm (LAT)). For 3D rotational angiography, 122 images were acquired from one single image run with the imaging system rotating 240° around the phantom's head (image intensifier 37 cm). RESULTS: Effective dose was 0.4 mSv for 2-plane DSA compared to 0.1 mSv for 3D rotational angiography. Organ doses were approximately two to five times higher for classical 2-plane technique compared to the 3D rotational angiography, respectively: brain (11.4 vs. 2.4 mSv), eye lens (4.5 vs.1 mSv), salivary glands (7 vs. 1,7 mSv), oral mucosa (2.7 vs.0.9 mSv), thyroid (0.5 vs. 0.2 mSv), thymus (0.2 vs. 0.05 mSv), bone marrow within imaged region (1 vs. 0.2 mSv), oesophagus (0.07 vs. 0.03 mSv), endotracheal system (2.6 vs. 0.7 mSv) and skeletal components in the imaged region (0.7 vs. 0.2 mSv). CONCLUSION: Three-dimensional rotational angiography clearly reduces radiation doses compared to the classical 2-plane technique. Replacement of additional 2-plane DSA projections with 3D rotational angiography will lead to a remarkable decrease in patient radiation dose, without loss of image quality. Thus, we recommend routine application of 3D rotational angiography, in particular for diagnostic assessment of aneurysm morphology.

Dynamic membrane structure induces temporal pattern formation.

The understanding of temporal pattern formation in biological systems is essential for insights into regulatory processes of cells. Concerning this problem, the present work introduces a model to explain the attachment/detachment cycle of MARCKS and PKC at the cell membrane, which is crucial for signal transduction processes. Our model is novel with regard to its driving mechanism: Structural changes within the membrane fuel an activator-inhibitor based global density oscillation of membrane related proteins. Based on simulated results of our model, phase diagrams were generated to illustrate the interplay of MARCKS and PKC. They predict the oscillatory behavior in the form of the number of peaks, the periodic time, and the damping constant depending on the amounts of MARCKS and PKC, respectively. The investigation of the phase space also revealed an unexpected intermediate state prior to the oscillations for high amounts of MARCKS in the system. The validation of the obtained results was carried out by stability analysis, which also accounts for further enhanced understanding of the studied system. It was shown, that the occurrence of the oscillating behavior is independent of the diffusion and the consumption of the reactants. The diffusion terms in the used reaction-diffusion equations only act as modulating terms and are not required for the oscillation. The hypothesis of our work suggests a new mechanism of temporal pattern formation in biological systems. This mechanism includes a classical activator-inhibitor system, but is based on the modifications of the membrane structure, rather than a reaction-diffusion system.

[Traumatic dissection of the carotid artery: challenges for diagnostics and therapy illustrated by a case example]. / Traumatische Karotisdissektion : Herausforderungen der Diagnostik und Therapie anhand eines Fallbeispiels.

Traumatic dissection of the carotid artery is an easily overlooked consequence of trauma with notable morbidity and mortality which can be observed in up to 4% of cases involving multiple trauma. Certain mechanisms and patterns of injury as well as specific symptoms should serve as indicators of a dissection and should therefore result in further diagnostic measures. An early diagnosis is of major relevance. This report describes the case of a 45-year-old victim of a traffic accident who showed symptoms of a dissection which had initially not been diagnosed.

HIV-1 drug resistant mutations in chronically infected treatment naive individuals in the pre-ARV era in Nigeria.

In Nigeria the Federal Government rolled out antiretroviral drugs for the management of HIV infection in year 2002. This study was carried out to determine the circulating antiviral drug mutations among ARV naïve patients with chronic HIV infection during the pre-ARV roll out era in the country. DNA was extracted from stored whole blood samples collected from 75 HIV positive patients attending the Medical outpatient clinic between December 1996 and November 2001. The Reverse transcriptase (RT) and the protease (PR) regions of the viral genome were amplified by nested PCR and then sequenced by cycle sequencing and analyzed using the ABI 3100 DNA sequencer to determine the mutations associated with protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI). Ten of the 64 (15.6%) samples with positive PCR had mutations for PR inhibitors (PI) including R8D, I 15V, G16E, M36I, M46L, L63P and H69K, while 5 of 63 harbored RT inhibitor (NRTI/NNRTI); V179I, A98T, V179E and A98S. Detection ofARV drug resistant mutations when ARV was not known to be in use in Nigeria calls for caution in the interpretation of drug resistance profile of HIV-1 from infected persons on treatment ARVs in the country.

Targeting the human DEAD-box polypeptide 3 (DDX3) RNA helicase as a novel strategy to inhibit viral replication.

Compounds currently used for the treatment of HIV-1 Infections are targeted to viral proteins. However, the high intrinsic mutation and replication rates of HIV-1 often lead to the emergence of drug resistant strains and consequent therapeutic failure. On this basis, cellular cofactors represent attractive new targets for HIV-1 chemotherapy, since targeting a cellular factor that is required for viral replication should help to overcome the problem of viral resistance. We and others have recently reported the identification of compounds suppressing HIV-1 replication by targeting the cellular DEAD-box helicase DDX3. These results provide a proof-of-principle for the feasibility of blocking HIV-1 infection by rendering the host cell environment less favorable for the virus. The rationale for such an approach and its implications in potentially overcoming the problem of drug resistance related to drugs targeting viral proteins will be discussed in the context of the known cellular functions of the DEAD-box helicase DDX3.

[Intratumoral Onyx embolisation in the management of juvenile nasopharyngeal angiofibroma]. / Intratumorale Onyx-Embolisation in der Therapie von juvenilen Nasenrachenangiofibromen.

Preoperative embolization for the treatment of juvenile nasopharyngeal angiofibroma was successfully accomplished with Onyx by intratumoral puncture for the first time. Extratumoral migration of Onyx particles was not observed, precluding the necessity to inflate the shield balloon. Postinterventional angiography showed complete occlusion of all supporting blood vessels. Transnasal surgery on the following day achieved complete resection of the angiofibroma without complications. Direct intratumoral embolization of juvenile nasopharyngeal angiofibromas appears to be a safe and effective preoperative method without complications. It could represent a new strategy for the treatment of JNA, as is already the case with other highly vascularized head and neck tumors. Moreover, it increases the likelihood of achieving complete resection.

[Direct percutaneous embolization of a carotid body tumor with Onyx]. / Perkutane Onyx(R)-Embolisation zur Therapie von Glomus-caroticum-Tumoren.

Carotid body tumors are highly vascularized lesions that require successful preoperative embolization to achieve favorable clinical results in terms of morbidity and complete tumor resection. The procedure of percutaneous embolization was performed using ethylene-vinyl alcohol copolymer (Onyx) in addition to balloon-catheter protection to prevent particle displacement into the internal carotid artery. The procedure resulted in nearly complete tumor embolization and facilitated the uneventful complete surgical resection. Percutaneous angiographic embolization of carotid body tumors in the head and neck was found to be safe and effective. This technique is likely to result in improved surgical outcomes and tumor resectability.

Percutaneous embolization of carotid paragangliomas using solely Onyx.

BACKGROUND AND PURPOSE: Paragangliomas are highly vascularized usually benign neoplasms arising from nerve tissue. Endovascular preoperative embolization is used to facilitate surgery but is often not complete, due to tiny feeding arteries not feasible for selective catheterization. Our purpose was to evaluate angiographic and clinical outcome using Onyx for percutaneous glomus tumor embolization. MATERIALS AND METHODS: A consecutive series of 4 patients with 6 paragangliomas located at the bifurcation of the common carotid artery were treated with percutaneous embolization using Onyx as the sole embolic material. RESULTS: Complete devascularization of the 6 paragangliomas was achieved using a percutaneous embolization technique with Onyx as a sole agent, combined with an endovascular microballoon that offered protection of the internal carotid artery. CONCLUSIONS: Further documentation is necessary to prove the higher grade of devascularization of paragangliomas with Onyx compared with other embolic material and the associated potential to facilitate surgery. Nevertheless, Onyx seems to be safe when used percutaneously due to its lavalike pattern flow and its controllable properties, allowing slow tumor bed penetration.

[Limb salvage for the diabetic foot - disease management program]. / Extremitätenerhalt für den diabetischen Fuss - Disease-Management-Programm.

OBJECTIVE: Lower-extremity amputation (LEA) is a common complication among patients with diabetes. This study tests the effects of a structured disease management program for the diabetic foot (DF) aiming to reduce the number of LEA. DESIGN, METHODS: In a prospective study design we investigate patients with DF in a system of outpatient treatment, acute in-patient care and rehabilitative treatment. Subjects were recruited since January 1(st), 2000, with the latest admission being December 31, 2004. All study participants undergo a five-year follow-up observation period. The University of Texas Wound Classification System (UT) of foot ulcers serves as basis of the documentation and analysis. We evaluated numbers of LEA, rates of ulcer healing and underlying forms of peripheral vascular disease. RESULTS: We report the results of the first patient group completing the two-year follow-up examination. In 2000, 102 subjects with new foot ulcers were consecutively included into the study. 68.6% were men, the mean age of the study population was 68.1 +/- 11.4 years and the mean diabetes duration was 19.4 +/- 10.3 years. After two years, 68 patients can still be examined. Altogether, 22 patients (21.6%) died, and 12 (11.8%) dropped out for various reasons. At the point of discharge from the clinics 35.3% of the ulcers had healed and another 44.1% were in UT grade 1. After two years, a complete healing could still be determined with 51 patients (50.0% of the cohort of the original 102 patients, or 75.0% of the subjects reaching the two-year follow-up). 10 subjects (9.8% or 14.5%) were in the UT grade 1. Eight diabetics underwent major amputation (MA) during the two-year examination period (amputation rate 7.8%). CONCLUSIONS: The primary objective of the study, a significant reduction of MA with DF patients, has been achieved. The ulcer healing rates are comparable to the reports of leading centers.

Application of the EIIP/ISM bioinformatics concept in development of new drugs.

The development of a new therapeutic drug is a complex, lengthy and expensive process. On average, only one out of 10,000 - 30,000 originally synthesized compounds will clear all the hurdles on the way to becoming a commercially available drug. The process of early and full preclinical discovery and clinical development for a new drug can take twelve to fifteen years to complete, and cost approximately 800 million dollars. The field of bioinformatics has become a major part of the drug discovery pipeline playing a key role in improvement and acceleration of this time and money consuming process. Here we reviewed the application of the EIIP/ISM bioinformatics concept for the development of new drugs. This approach, connecting the electron-ion interaction potential of organic molecules and their biological properties, can significantly reduce development time through (i) identification of promising lead compounds that have some activity against a disease by fast virtual screening of the large molecular libraries, (ii) refinement of selected lead compounds in order to increase their biological activity, and (iii) identification of domains of proteins and nucleotide sequences representing potential targets for therapy. Special attention is paid in this review to the application of the EIIP/ISM bioinformatics platform along with other experimental techniques (screening of a phage displayed peptide libraries, testing selected peptides and small molecules for antiviral activity in vitro) in development of HIV entry inhibitors, representing a new generation of the AIDS drugs.

Endovascular treatment of trigeminal neuralgia caused by arteriovenous malformation: is surgery really necessary?

A case is presented with secondary trigeminal neuralgia (TN) caused by an arteriovenous malformation (AVM) of the cerebellopontine cistern, which was detected by radiological work-up for planned microvascular decompression. An AVM surrounding the trigeminal nerve was demonstrated on thin-slice heavily T (2)-weighted 3D-sequence on magnetic resonance imaging (MRI) and confirmed by angiography. The first therapeutic step was endovascular embolization with complete obliteration of the AVM and cessation of pain. Nevertheless surgical excision was performed in order to remove compressive vessels and to prevent a recurrence of pain.

Program sustainability of a community-based intervention to prevent falls among older Australians.

Multi-strategy interventions have been demonstrated to prevent falls among older people, but studies have not explored their sustainability. This paper investigates program sustainability of Stay on Your Feet (SOYF), an Australian multi-strategy falls prevention program (1992-1996) that achieved a significant reduction in falls-related hospital admissions. A series of surveys assessed recall, involvement and current falls prevention activities, 5 years post-SOYF, in multiple original SOYF stakeholder groups within the study area [general practitioners (GPs), pharmacists, community health (CH) staff, shire councils (SCs) and access committees (ACs)]. Focus groups explored possible behavioural changes in the target group. Surveys were mailed, except to CH staff and ACs, who participated in guided group sessions and were contacted via the telephone, respectively. Response rates were: GPs, 67% (139/209); pharmacists, 79% (53/67); CH staff, 63% (129/204); SCs, 90% (9/10); ACs, 80% (8/10). There were 73 older people in eight focus groups. Of 117 GPs who were practising during SOYF, 80% recalled SOYF and 74% of these reported an influence on their practice. Of 46 pharmacists operating a business during SOYF, 45% had heard of SOYF and 79% of these reported being 'somewhat' influenced. Of 76 community health staff (59%) in the area at that time, 99% had heard of SOYF and 82% reported involvement. Four SCs retained a SOYF resource, but none thought current activities were related. Seven ACs reported involvement, but no activities were sustained. Thirty-five focus group participants (48%) remembered SOYF and reported a variety of SOYF-initiated behaviour changes. Program sustainability was clearly demonstrated among health practitioners. Further research is required to assess long-term effect sustainability.

Ocular manifestation of disseminated Mycobacterium simiae infection in a cat.

Disseminated mycobacterial disease was diagnosed in an eight-year-old domestic shorthaired cat, with involvement of the skin, lungs, lymph nodes and one eye. Mycobacterium simiae was cultured from skin biopsies on solid agar and in liquid media. This organism is known to cause pulmonary, cutaneous or disseminated infection in human patients with acquired immunodeficiency syndrome but has never been encountered as a pathogen in companion animals. Combination treatment with rifampicin, enrofloxacin and clarithromycin resulted in complete clinical remission within six months, with no side effects. No recurrence was observed in a 22-month follow-up period.