MIBG-SPECT/CT-angiography with 3-D reconstruction of an extra-adrenal phaeochromocytoma with dissection of an aortic aneurysm.
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3-Iodobenzylguanidine↗
Biomedical subjects
M Weber
Publications and source records attributed to M Weber.
Morphometric analysis of the retina from horses infected with the Borna disease virus.
Borna disease (BD) is a fatal disorder of horses, often characterized by blindness. Although degeneration of retinal neurons has been demonstrated in a rat model, there are controversial data concerning whether a similar degeneration occurs in the retina of infected horses. To investigate whether BD may cause degeneration of photoreceptors and possibly of other neuronal cells at least at later stages of the disease, we performed a detailed quantitative morphologic study of retinal tissue from Borna-diseased horses. BD was diagnosed by detection of pathognomonic Joest-Degen inclusion bodies in the postmortem brains. Paraffin sections of paraformaldehyde-fixed retinae were used for histologic and immunohistochemical stainings. Numbers of neurons and Müller glial cells were counted, and neuron-to-Müller cell ratios were calculated. Among tissues from 9 horses with BD, we found retinae with strongly altered histologic appearance as well as retinae with only minor changes. The neuron-to-Müller cell ratio for the whole retina was significantly smaller in diseased animals (8.5 +/- 0.4; P < .01) as compared with controls (17.6 +/- 0.8). It can be concluded that BD in horses causes alterations of the retinal histology of a variable degree. The study provides new data about the pathogenesis of BD concerning the retina and demonstrates that a loss of photoreceptors may explain the observed blindness in infected horses.
Animals↗
Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium.
Previous studies have tested gene replacement therapy in RPE65-deficient dogs using recombinant adeno-associated virus 2/2 (rAAV2/2), -2/1 or -2/5 mediated delivery of the RPE65 gene. They all documented restoration of dark- and light-adapted electroretinography responses and improved psychophysical outcomes. Use of a specific RPE65 promoter and a rAAV vector that targets transgene expression specifically to the RPE may, however, provide a safer setting for the long-term therapeutic expression of RPE65. Subretinal injection of rAAV2 pseudotyped with serotype 4 (rAAV2/4) specifically targets the RPE. The purpose of our study was to evaluate a rAAV2/4 vector carrying a human RPE65cDNA driven by a human RPE65 promoter, for the ability to restore vision in RPE65-/- purebred Briard dogs and to assess the safety of gene transfer with respect to retinal morphology and function. rAAV2/4 and rAAV2/2 vectors containing similar human RPE65 promoter and cDNA cassettes were generated and administered subretinally in eight affected dogs, ages 8-30 months (n = 6 with rAAV2/4, n = 2 with rAAV2/2). Although fluorescein angiography and optical coherence tomography examinations displayed retinal abnormalities in treated retinas, electrophysiological analysis demonstrated that restoration of rod and cone photoreceptor function started as soon as 15 days post-injection, reaching maximal function at 3 months post-injection, and remaining stable thereafter in all animals treated at 8-11 months of age. As assessed by the ability of these animals to avoid obstacles in both dim and normal light, functional vision was restored in the treated eye, whereas the untreated contralateral eye served as an internal control. The dog treated at a later age (30 months) did not recover retinal function or vision, suggesting that there might be a therapeutic window for the successful treatment of RPE65-/- dogs by gene replacement therapy.
Animals↗
Postinjury vascular intimal hyperplasia in mice is completely inhibited by CD34+ bone marrow-derived progenitor cells expressing membrane-tethered anticoagulant fusion proteins.
BACKGROUND: Coagulation proteins promote neointimal hyperplasia and vascular remodelling after vessel injury, but the precise mechanisms by which they act in vivo remain undetermined. OBJECTIVES: This study, using an injury model in which the neointima is derived from bone marrow (BM)-derived cells, compared inhibition of tissue factor or thrombin on either BM-derived or existing vascular smooth muscle cells. METHODS: Two transgenic (Tg) mouse strains expressing membrane-tethered tissue factor pathway inhibitor (TFPI) or hirudin (Hir) fusion proteins driven by an alpha smooth muscle actin (SMA) promoter were generated (alpha-TFPI-Tg and alpha-Hir-Tg) and the phenotype after wire-induced endovascular injury was compared with that in wild-type (WT) controls. RESULTS: WT mice developed progressive neointimal expansion, whereas injury in either Tg was followed by repair back to a preinjured state. This was also seen when WT mice were reconstituted with BM from Tg mice but not when Tgs were reconstituted with WT BM, in which injury was followed by slowly progressive neointimal expansion. Injection of CD34+ cells from Tg mice into injured WT mice resulted in the accumulation of fusion protein-expressing cells from day 3 onwards and an absence of neointimal hyperplasia in those areas. CONCLUSIONS: Neointimal development after wire-induced endovascular injury in mice was completely inhibited when BM-derived cells infiltrating the damaged artery expressed membrane tethered anticoagulant fusion proteins under an alpha-SMA promoter. These findings enhance our understanding of the pathological role that coagulation proteins play in vascular inflammation.
Animals↗
Prognostic value of N-terminal pro-B-type natriuretic peptide for conservatively and surgically treated patients with aortic valve stenosis.
OBJECTIVE: To evaluate the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with aortic stenosis being treated conservatively or undergoing aortic valve replacement (AVR). METHODS: 159 patients were followed up for a median of 902 days. 102 patients underwent AVR and 57 were treated conservatively. NT-proBNP at baseline was raised in association with the degree of severity and of functional status. RESULTS: During follow up 21 patients (13%) died of cardiac causes or required rehospitalisation for decompensated heart failure. NT-proBNP at baseline was higher in patients with an adverse outcome than in event-free survivors (median 623 (interquartile range 204-1854) pg/ml v 1054 (687-2960) pg/ml, p = 0.028). This difference was even more obvious in conservatively treated patients (331 (129-881) pg/ml v 1102 (796-2960) pg/ml, p = 0.002). Baseline NT-proBNP independently predicted an adverse outcome in the entire study group and in particular in conservatively treated patients (area under the curve (AUC) = 0.65, p = 0.028 and AUC = 0.82, p = 0.002, respectively) but not in patients undergoing AVR (AUC = 0.544). At a cut-off value of 640 pg/ml, baseline NT-proBNP was discriminative for an adverse outcome. CONCLUSION: NT-proBNP concentration is related to severity of aortic stenosis and provides independent prognostic information for an adverse outcome. However, this predictive value is limited to conservatively treated patients. Thus, the data suggest that assessing NT-proBNP may have incremental value for selecting the optimal timing of valve replacement.
Aged↗
[Predictive value of an ischemia test in men and women with stable angina pectoris in clinical practice. Results of the heart catheter registry of the Working Society of Senior Hospital Cardiologists].
BACKGROUND AND OBJECTIVE: Symptoms of coronary artery disease (CAD) and the accuracy of non-invasive tests differ between men and women. This study sought to evaluate the difference between the predictive value of a stress test in clinical practice for the diagnosis of significant coronary heart disease (CHD: stenosis > 50%) between women and men with stable angina. PATIENTS AND METHODS: 143,848 consecutive patients undergoing diagnostic coronary angiography at 99 hospitals during 2002 were included in the prospective cardiac catheter registry of the Working Party of Senior Hospital Cardiologists (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte [ALKK]). All patients with stress test and stable angina CCS class I-III (n=27387; 20.4%) were included, 10,911 (39.8%) of them female. 70.6% of women and 73.2% of men had a positive stress test. RESULTS: In 46.1% of women and 71.5% of men with positive test and stable angina had relevant CHD (p<0,001). Diabetes increased the prevalence of CHD in patients with a positive test both in women (65.5%) and men (80.5%), with CCS class III angina to 63.3% and 85.8%, respectively. CONCLUSIONS: In clinical practice a positive stress test in women with stable angina is associated significantly less often with clinically relevant CHD than in men. The low positive predictive value of 46.1% underlines the need for additional clinical features like diabetes or cardiac symptoms (CCS class) before invasive diagnosis is performed.
Adult↗
B cell ligand discrimination through a spreading and contraction response.
B cells recognize foreign antigens by virtue of cell surface immunoglobulin receptors and are most effectively activated by membrane-bound ligands. Here, we show that in the early stages of this process, B cells exhibit a two-phase response in which they first spread over the antigen-bearing membrane and then contract, thereby collecting bound antigen into a central aggregate. The extent of this response, which is both signaling- and actin-dependent, determines the quantity of antigen accumulated and hence the degree of B cell activation. Brownian dynamic simulations reproduce essential features of the antigen collection process and suggest a possible basis for affinity discrimination. We propose that dynamic spreading is an important step of the immune response.
Actins↗
Coherent combination of high-power, zigzag slab lasers.
We demonstrate a scalable architecture for a high-power, high-brightness, solid-state laser based on coherent combinations of master oscillator power amplifier chains. A common master oscillator injects a sequence of multikilowatt Nd:YAG zigzag slab amplifiers. Adaptive optics correct the wavefront of each amplified beamlet. The beamlets are tiled side by side and actively phase locked to form a single output beam. The laser produces 19 kW with beam quality <2x diffraction limited. To the best of our knowledge, this is the brightest cw solid-state laser demonstrated to date.
Journal Article↗
Prior therapy with antiplatelet agents is not associated with outcome in patients with acute ischemic stroke/TIA.
BACKGROUND AND PURPOSE: It is unclear whether prior therapy with antiplatelet agents (APA) is associated with a better outcome in patients with acute ischemic cerebrovascular events. METHODS: Within a multi-center cross-sectional study, nested in a cohort we analyzed the relation between prior therapy with APA and stroke severity in 1643 patients with acute ischemic stroke or TIA. Clinical severity of the vascular event was evaluated by the National Institutes of Health Stroke Scale on admission (NIHSS1) and after 1 week (NIHSS2). By means of analysis of variance we analyzed a possible association of APA with stroke severity and interactions regarding stroke severity between APA and other clinical measures. RESULTS: 475 patients (29 %) received aspirin prior to the cerebrovascular event, 51 patients (3 %) ticlopidine or clopidogrel and 26 patients (1.6%) aspirin combined with extended release dipyridamole. 66% (1091) of patients did not take any antiplatelet medication. Neither the NIHSS1 nor the NIHSS2 nor the change of stroke severity between these time points (NIHSS1- NIHSS2) was associated with prior APA medication. We did not find significant interactions between APA use and clinical measures regarding stroke severity. CONCLUSIONS: Our results do not indicate that prior therapy with APA is associated with a better outcome in acute ischemic cerebrovascular events. There were no interactions found with other features that were associated with stroke severity.
Aged↗
Release pattern of N-terminal pro B-type natriuretic peptide (NT-proBNP) in acute coronary syndromes.
BACKGROUND: Recently it has been found that BNP and NT-proBNP provide independent prognostic information in patients with acute coronary syndromes (ACS). However, little data are available on the time course of NT-proBNP levels in relation to onset of symptoms. METHODS AND RESULTS: We included 765 patients (236 females, aged 64 +/- 11 years) with an ACS (STEMI 42%, NSTEMI 41%, UAP 17%), who were referred for coronary angiography. NT-proBNP was assessed on admission and the next day. NT-proBNP values were related to the time duration from onset of symptoms until blood drawing with lowest values within 3 h and highest values 24-36 h after onset of symptoms (147 (64-436) pg/ml and 1099 (293-3795) pg/ml, respectively, p < 0.001). Highest values for NT-proBNP on admission were found in patients with NSTEMI compared to patients with STEMI and UAP (912 (310-2258) pg/ml) vs 262 (85-1282) pg/ml) vs 182 (74- 410) pg/ml; p < 0.001), but no difference was present between STEMI and NSTEMI the day after admission (1325 (532-2974) pg/ ml vs 1169 (555-3413) pg/ml; p = 0.676). In contrast NT-proBNP values remained unchanged in UAP (182 (74-410) pg/ml) vs 171 (53-474) pg/ml). CONCLUSION: The time interval from onset of symptoms to first blood collection is an important determinant for NT-proBNP values on admission in patients with an ACS and needs to be considered in clinical practice.
Angina, Unstable↗
[Symptomatic management in amyotrophic lateral sclerosis (ALS)].
Although disease-specific treatment of amyotrophic lateral sclerosis is still unsatisfactory, a number of advances have been made in the symptomatic therapy of ALS patients within the last decade. Current data suggest that active and aggressive multidisciplinary management of ALS patients improve their quality of life and prolong their survival. Patient and caregiver communications and decisions are increasingly recognized to be a relevant part of this management. A wide range of supportive and palliative measures, in particular the widely use of symptomatic drugs for pseudobulbar affect, sialorrhea, and sleep disorders is available to relieve patients symptomatology. In addition, patients quality of life has been profoundly improved by the introduction of enteral nutrition and non-invasive ventilation.
Disease Progression↗
Increased polysialic acid neural cell adhesion molecule expression in human hippocampus of heroin addicts.
Chronic exposure to heroin is known to cause cognitive deficits. However, little is known about the underlying molecular mechanisms. It has been suggested that opiate-induced neurotoxicity as well as impaired plasticity and regeneration may be relevant. One of the target regions where regeneration still can be observed in the adult brain is the hippocampus. Since polysialic acid neural cell adhesion molecule is regarded as one of the key players involved in plasticity and regeneration of neural tissue, we analyzed polysialic acid neural cell adhesion molecule expression in the fascia dentate hilus of the human hippocampus of 29 lethally intoxicated heroin addicts and matched controls. Immunohistochemistry with an antibody directed against polysialic acid neural cell adhesion molecule revealed its expression in differently sized cells which could be identified as neurons and glial cells. We observed an increase in the percentage of polysialic acid neural cell adhesion molecule positive neurons in hippocampal hilus of heroin addicts compared with controls (P = 0.001).Interestingly, we also observed polysialic acid neural cell adhesion molecule expression in glial cells as evidenced by double immunofluorescence with glial fibrillary acidic protein and polysialic acid neural cell adhesion molecule using confocal laser scanning microscopy. The fraction of polysialic acid neural cell adhesion molecule positive glial cells was also higher in heroin addicts compared with controls (P = 0.009). In addition, within the group of addicts morphine blood concentrations showed a positive correlation with the percentage of polysialic acid neural cell adhesion molecule positive neurons (P = 0.04; r = 0.547). In conclusion, we observed an increase in polysialic acid neural cell adhesion molecule positive neurons and glial cells in hippocampi of heroin addicts. This might reflect an attempt to repair cell damage due to heroin exposure.
Adolescent↗
Bariatric surgery - a successful way to battle the weight crisis.
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Bariatrics↗
[Water and electrolyte disturbances in critical care].
Management of critically ill patients regularly involves the treatment of water and electrolyte disturbances. Moreover, critical care itself may contribute to volume overload and electrolyte abnormalities. Initial therapy should be followed by consequent diagnostic evaluation. The shift of volume and potassium in severe pancreatitis, for example, may lead to a life-threatening situation. In brain-dead patients, successful organ donation is facilitated by careful maintenance of water and electrolyte homeostasis.
Critical Care↗
[Surgical extraction of wisdom teeth].
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Germany↗
[How to perform intravitreal injections].
Drugs to treat retinal diseases are often injected intravitreally. This procedure can cause severe complications. We present ways to minimize the risk for complications. Rigorous preoperative antisepsis with povidone iodine, a sterile environment (using gloves and a mask for the injector, a lid speculum, and a drape on the eye to be injected), and immediate follow-up after injection are key issues of the injection technique.
Humans↗
[Amniotic membrane transplantation and limbic-conjunctival autograft for recurrent pterygium, either invasive or with optic axis involvement].
OBJECTIVE: To evaluate amniotic membrane transplantation with limbic-conjunctival autograft during recurrent pterygium surgery in cases with a risk of stromal defect or with optic axis involvement, in order to limit the corneal defect in pterygium and preserve vision with moderate astigmatism. MATERIALS AND METHODS: Retrospective study of 50 cases. Three clinical aspects were encountered: A, recurrent pterygium after simple surgery (a corrected stromal defect)--six cases; B, primary pterygium at risk of stromal defect - five cases; C, primary pterygium with optic axis involvement--four cases. Each patient underwent ablative surgery followed by ocular surface rebuilding with limbic-conjunctival autograft combined with amniotic membrane graft on the corneal defect. Visual acuity and astigmatism were measured and compared before and after surgery. RESULTS: The mean follow-up was 13 months. At the end of the follow-up, the recurrence rate was 27% (four cases: two in A, two in B, and none in C). Mean visual acuity was improved from 0.7 to 0.8 postoperatively (p=0.041). Astigmatism changed slightly from 1.47 to 1.98 dioptres (p=0.155). DISCUSSION: For recurrent pterygium, with stromal defect or optic axis involvement, amniotic membrane transplantation and limbic-conjunctival autograft seems not to influence the recurrence rate. However, by limiting initial keratectomy, this surgical procedure only slightly modifies visual acuity and astigmatism in the cases where the two parameters are slightly affected. Failure can be easily managed with further surgery such as lamellar keratoplasty. CONCLUSION: Amniotic membrane transplantation and limbic-conjunctival autograft for recurrent pterygium or with optic axis involvement can be useful to integrate in the therapeutic arsenal of pterygium surgery.
Adult↗
[Familial primary pulmonary hypertension revealed by the association of bilateral chemosis, subacute myopia, and exophthalmos].
PURPOSE: To report a rare case of primary pulmonary hypertension (PPH) revealed by a relapsing chemosis, exophthalmos, and subacute myopia. PATIENTS AND METHODS: A 46-year-old woman presented with recurrent bouts of chemosis, exophthalmos, and subacute myopia. Her visual troubles were triggered by physical effort. She had a history of a longstanding high blood pressure that was noncompliant to all conventional hypotensive therapy. Automated refraction under cycloplegia showed recent myopia. At observation she had a bilateral, moderate chemosis. Hertel exophthalmometer measured a symmetric exophthalmos of 23 mm. Intraocular pressure was 20 mmHg OD and 24 mmHg OS. Eye fundus was strictly normal. RESULTS: Laboratory analysis showed no thyroid or inflammatory disease. HIV serology was negative as were antinuclear antibodies. Orbital CT confirmed the axial, symmetric exophthalmos. Echocardiogram brought out the diagnosis of PPH. Genetic studies by PCR localized the BMPR2 mutation that is characteristic of the familial type of PPH. Symptoms decreased under treatment. DISCUSSION: PPH is a rare disease caused by thickening of the arteriolar walls in the pulmonary bed, which results in a right-heart hypertension with venous stasis. Many authors have reported different posterior segment diseases secondary to PPH. However, anterior segment manifestations are extremely rare. These may be caused by a ciliary body congestion and retrobulbar vasodilatation. CONCLUSION: The association of chemosis, exophthalmos, and subacute myopia is unusual in PPH. We recommend keeping in mind the PPH as a differential diagnosis in those cases, especially in patients who suffer from high blood pressure.
Conjunctival Diseases↗