Orbital Cavernous Venous Malformation in a 35-Year-Old Man: A Case Report.

In this article we present a case of a 35-year-old patient with a massive 43 × 35 × 34 mm cavernous venous malformation of the left orbit. The orbital lesion was initially observed in 2008 and remained untreated to 2021 due to the patient's refusal to consent to the surgical procedure; which caused the tumor to grow to monstrous dimensions.

Respiratory function in pregnant women.

Respiratory disorders during pregnancy are connected with its physiology. About half of pregnant women suffer from dyspnea on exertion and some 20 % also from dyspnea at rest. Symptoms may intensify in obese patients. Smoking and respiratory disorders influence the well-being of the fetus. This study evaluates respiratory function in pregnant women as assessed by spirometry. The tests were carried out in 54 pregnant women in the 2nd and 3rd trimester. We found reduced values of vital capacity and expiratory reserve volume in all women, which suggests the existence a restrictive respiratory disorder in physiological pregnancy. Smoking seems to cause obstructive disorders; in smoking patients there was a reduction of the Tiffenau ratio. Participation in birth classes had a positive influence on inspiratory capacity. High BMI before pregnancy, excessive weight gain during pregnancy, or age of becoming pregnant did not appreciably influence spirometry results.

Bupivacaine crystal deposits after long-term epidural infusion.

The case of a 45-year-old male patient (body weight 52 kg, height 1.61 m) with a locally invasive gastric carcinoma infiltrating into the retroperitoneal space is reported. Because of severe cancer pain a tunnelled thoracic epidural catheter (EC) was placed at thoracic spinal level 7/8 and a local anesthetic (LA) mixture of bupivacaine 0.25 % and morphine 0.005 % was infused continuously at 6 ml h(-1). To optimize pain therapy the concentration was doubled (bupivacaine 0.5 %, morphine 0.01 %) 3 months later but the infusion rate was reduced to 3 ml h(-1) thus the total daily dose did not change. The patient died 6 months after initiation of the epidural analgesia from the underlying disease. The total amount of bupivacaine infused was 69 g and of morphine 1.37 g. The patient never reported any neurological complications. The autopsy revealed large white crystalline deposits in the thoracic epidural space which were identified as bupivacaine base by infrared spectrometry. Morphine could not be detected. A histological examination showed unreactive fatty tissue necrosis within the crystalline deposits but nerve tissue could not be identified. It is concluded that the bupivacaine crystalline deposits arose due to precipitation but the clinical significance with regard to sensory level and neuraxial tissue toxicity is unknown.

A functional outcome study comparing total ankle arthroplasty (TAA) subjects with pain to subjects with absent level of pain by means of videofluoroscopy.

BACKGROUND: Total ankle arthroplasty (TAA) subjects often suffer pain on the anteromedial side of their ankle joint. Whether this prevalent pain is caused by a changed motion pattern of the TAA is unclear. Therefore, this study assessed the kinematic differences in the motion of the TAA components during gait, comparing TAA subjects with elevated versus absent levels of pain. METHODS: Eleven TAA subjects (5 with pain vs. 6 without pain), all with unilateral Mobility™ TAA and at least two years post-operation, were recruited and stratified based on standard clinical assessed patient data. The 3D motion of the TAA was assessed by means of videofluoroscopy during level, uphill and downhill walking. RESULTS: The hypothesis that the pain group shows a different kinematic motion pattern than the no pain group could not be confirmed. CONCLUSIONS: The same kinematic motion pattern causes pain in some patients, but not in others. Further investigation concerning ligament stresses is needed.

Comparison of reference points in different methods of temporomandibular joint imaging.

PURPOSE: Conventional radiography is a well-established method for imaging of the temporomandibular joint (TMJ) structures. However, the dental computer tomography becomes more important for the visualization of teeth in the jaw-bone. The applicability of dental computer tomography for the visualization of the TMJ it not yet been proven. The aim of the study was to identify TMJ structures using reference points with the magnetic resonance imaging (MRI) and the computed tomography (CT). METHODS: In order to compare the visualization and measurement of the TMJ a total of eight human cadaver heads was examined with CT and MRI and analysed using reference points. RESULTS: In both imaging techniques the selected reference points and distances are well definable and allow objective evaluation of anatomical structures. The CT images display a clearly better contrast to noise ratio than the MR images. The distance measurement of different width and length showed significant correlation of both images techniques. CONCLUSIONS: In TMJ diagnostics, maximum information could be obtained using both imaging techniques together due to synergistic effects.

3D representation of the surface topography of normal and dysplastic trochlea using MRI.

The three-dimensional (3D) image of the articular surface topography of the normal and the dysplastic trochlea has not been defined. The aim of this study was to represent both the normal and dysplastic trochlear geometry in 3D using magnetic resonance imaging (MRI). Using the segmentation software program Amira (Mercury Computer Systems, Inc., Chelmsford, USA) we created 3D reconstructions of the distal femur bone and cartilage using MRI scans. Bone and cartilage of the distal femur were traced slice by slice in the acquisitioned dimension while the Amira program reconstructed the 3D model. This model was then transferred to the Rhinoceros 4.0 software (Robert McNeel & Associates, Seattle, USA) for measuring. Using this system a non-invasive 3D representation of the articular cartilage and bone of the normal trochlea and depiction of different types of trochlear dysplasia were possible. Potential advantages of these MRI measurements are assessment of the 3D articular cartilage of the whole trochlea and the bony contours on the same image, no imaging errors from joint malpositioning, no ionizing radiation, precise preoperative planning according to the documented pathomorphology, and comparison between the preoperative and the postoperative shapes. The disadvantages include higher costs compared to radiography or CT scans, and time consuming reconstruction, making them currently a research tool.

Innate immune defenses induced by CpG do not promote vaccine-induced protection against foot-and-mouth disease virus in pigs.

Emergency vaccination as part of the control strategies against foot-and-mouth disease virus (FMDV) has the potential to limit virus spread and reduce large-scale culling. To reduce the time between vaccination and the onset of immunity, immunostimulatory CpG was tested for its capacity to promote early protection against FMDV challenge in pigs. To this end, CpG 2142, an efficient inducer of alpha interferon, was injected intramuscularly. Increased transcription of Mx1, OAS, and IRF-7 was identified as a sensitive measurement of CpG-induced innate immunity, with increased levels detectable to at least 4 days after injection of CpG formulated with Emulsigen. Despite this, CpG combined with an FMD vaccine did not promote protection. Pigs vaccinated 2 days before challenge had disease development, which was at least as acute as that of unvaccinated controls. All pigs vaccinated 7 days before challenge were protected without a noticeable effect of CpG. In summary, our results demonstrate the caution required when translating findings from mouse models to natural hosts of FMDV.

The effect of treatment with fentanyl patches on pain relief and improvement in overall daily functioning in patients with postherpetic neuralgia.

Postherpetic neuralgia often causes persistent pain, which can compromise patients' quality of life. The aim of the study was to examine the effect of pain reduction after the application of transdermal fentanyl on the quality of life of patients with postherpetic neuralgia. The study lasted 12 weeks. The study population included adult patients experiencing spontaneous pain, expressed by 4 points on the pain numeric rating scale (NRS). To assess quality of life questionnaire SF-36, the Zung depression scale and NRS were used. Pharmacotherapy included amitryptyline (Amitriptylinum VP) 10 mg orally once daily, gabapentine (Gabapentin TEVA 100 mg) 200-900 mg/24 hour orally twice daily and fentanyl skin patches (Durogesic) 12.5-100 microg/hour. Thirty four patients were qualified for the study. Comparison of pain intensity before the treatment and after 12 weeks showed that all the patients experienced relief. The treatment evidently reduced limitations in the physical and social domains. There was little improvement in the general physical capacity and mental condition. Analysis of correlation between changes in quality of life in the emotional, physical and social domains revealed that they were strongly interlinked. Increase in physical activity was accompanied by positive changes in the mental condition, better general wellbeing was correlated with increased social activity, and increased social activity was accompanied by improved physical condition. The more effective the treatment was, the more evident was improvement in the patients' quality of life in the physical, social and mental domains.

Efficacy of healing process of bone defects after apicectomy: results after 6 and 12 months.

The aim of this study was to assess the efficacy of selected surgical treatment techniques of bone defects after apectomy. A total of 106 postresection bone defects, located in maxilla and mandible were included in the study: the defects were treated with resorbable collagen membrane (BG I- 26 defects), xenogenic bovine material (BOC II- 30 defects) and xenogenic bovine material with platelet rich plasma (BOC/PRP III- 20 defects). In the control group the defects were left to heal spontaneously. Clinical and radiological assessment was performed at 6 and 12 months after the procedures. The analysis among groups revealed higher efficiency of the method of treatment that uses guide bone regeneration in comparison to the group in both post-operative control periods. After 6 months, the differences were statistically significant for each group using the regeneration methods, but after 12 months only for the BOC/PRP group. Treatment using selected guided bone regeneration techniques proved superior to the control group in both observation periods, but after 6 as well 12 months the best results in the BOC/PRP group were observed.

Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40.

SGN-40 is a therapeutic antibody targeting CD40, which induces potent anti-lymphoma activities via direct apoptotic signalling cells and by cell-mediated cytotoxicity. Here we show antibody-dependent cellular phagocytosis (ADCP) by macrophages to contribute significantly to the therapeutic activities and that the antitumour effects of SGN-40 depend on Fc interactions.

[Development of a soft tissue ulcer after long-term peridural infusion]. / Entwicklung eines Weichteilulkus nach periduraler Langzeitinfusion.

Local anaesthetic agents (LA) in clinical concentrations have the potential for tissue toxicity, although this is rarely observed in clinical practice. The case of a 74-year-old female patient (BMI 16.8 kg/m(2)) with a metastasising bronchial carcinoma is reported, who suffered from severe back pain due to tumour infiltration. For pain management a tunnelled continuous thoracic peridural catheter (PC) was placed and a mixture of bupivacaine 0.49%, morphine 0.0036% and clonidine 0.0001% was infused at 3 ml/h. After 8 weeks of continuous infusion an ulcer developed in the soft tissue close to the thoracic spine containing whitish crystalline material (CM). A computed tomography examination revealed a subcutaneously displaced PC with extensive fluid collection reaching down to the sacrospinalis muscle. Histologically an unreactive necrosis with enclosed CM of unknown etiology was found. The result of the chemical analysis of the deposits demonstrated bupivacaine, morphine and sodium chloride. It is concluded that the soft tissue ulcer was probably caused by precipitation of the LA mixture.

[Quality assurance in geriatrics--opportunities and risks involved in the current health care reform in Germany]. / Qualitätssicherung in der Geriatrie - Chancen und Risiken der aktuellen Gesundheitsreform (GKV-Wettbewerbsstärkungsgesetz).

Geriatrics is needed as an independent discipline to cope with the demographic challenges ahead in a medically qualified manner. Geriatrics is a "supraspeciality" and not a "subspeciality" of Internal Medicine, because geriatrics typically combines the different medical disciplines and does not play a role as an independent functional area. For general practitioners and medical specialists a geriatric qualification is required. The geriatric structures in place in the German federal states need to be adapted and advanced with a focus on ambulatory geriatric service provision. The current health care reform has resulted in a strengthening of rehabilitation in general and in particular of an ambulant/mobile service approach. The resultant opportunities and risks are described. Internal and external quality assurance is indispensable for the advancement of structures including geriatrics and social medicine.

CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers.

CD133/prominin-1 is a pentaspan transmembrane glycoprotein overexpressed in various solid tumours including colorectal and glioblastomas. CD133 was found here to be highly expressed in >or=50% of pancreatic, gastric and intrahepatic cholangiocarcinomas. Quantitative flow cytometric analysis showed that a panel of established hepatocellular, pancreatic and gastric cancer cell lines expressed CD133 at levels higher than normal epithelial cells or bone marrow progenitor cells. A murine anti-human CD133 antibody (AC133) conjugated to a potent cytotoxic drug, monomethyl auristatin F (MMAF), effectively inhibited the growth of Hep3B hepatocellular and KATO III gastric cancer cells in vitro with IC(50) values of 2-7 ng ml(-1). MMAF induced apoptosis in the cancer cells as measured by caspase activation. The anti-CD133-drug conjugate (AC133-vcMMAF) was shown to internalise and colocalised with the lysosomal marker CD107a in the sensitive cell lines. In contrast, in the resistant cell line Su.86.86, the conjugate internalised and colocalised with the caveolae marker, Cav-1. Addition of ammonium chloride, an inhibitor of lysosomal trafficking and processing, suppressed the cytotoxic effect of AC133-vcMMAF in both Hep3B and KATO III. Anti-CD133-drug conjugate treatment resulted in significant delay of Hep3B tumour growth in SCID mice. Anti-CD133 antibody-drug conjugates warrant further evaluation as a therapeutic strategy to eradicate CD133+ tumours.

A new method for the noninvasive determination of abdominal muscle feedforward activity based on tissue velocity information from tissue Doppler imaging.

Rapid arm movements elicit anticipatory activation of the deep-lying abdominal muscles; this appears modified in back pain, but the invasive technique used for its assessment [fine-wire electromyography (EMG)] has precluded its widespread investigation. We examined whether tissue-velocity changes recorded with ultrasound (M-mode) tissue Doppler imaging (TDI) provided a viable noninvasive alternative. Fourteen healthy subjects rapidly flexed, extended, and abducted the shoulder; recordings were made of medial deltoid (MD) surface EMG and of fine-wire EMG and TDI tissue-velocity changes of the contralateral transversus abdominis, obliquus internus, and obliquus externus. Muscle onsets were determined by blinded visual analysis of EMG and TDI data. TDI could not distinguish between the relative activation of the three muscles, so in subsequent analyses only the onset of the earliest abdominal muscle activity was used. The latter occurred <50 ms after the onset of medial deltoid EMG (i.e., was feedforward) and correlated with the corresponding EMG onsets (r = 0.47, P < 0.0001). The mean difference between methods was 20 ms and was likely explained by electromechanical delay; limits of agreement were wide (-40 to +80 ms) but no greater than those typical of repeated measurements using either technique. The between-day standard error of measurement of the TDI onsets (examined in 16 further subjects) was 16 ms. TDI yielded reliable and valid measures of the earliest onset of feedforward activity within the anterolateral abdominal muscle group. The method can be used to assess muscle dysfunction in large groups of back-pain patients and may also be suitable for the noninvasive analysis of other deep-lying or small/thin muscles.

[Nausea and vomiting in the postoperative phase. Expert- and evidence-based recommendations for prophylaxis and therapy]. / Ubelkeit und Erbrechen in der postoperativen Phase. Experten- und evidenzbasierte Empfehlungen zu Prophylaxe und Therapie.

There are no consensus guidelines for the management of postoperative nausea and vomiting (PONV) in German speaking countries. This meeting was intended to develop such guidelines on which individual health care facilities can derive their specific standard operating procedures (SOPs). Anesthesiologists reviewed published literature on key topics which were subsequently discussed during two meetings. It was emphasized that recommendations were based on the best available evidence. The clinical relevance of individual risk factors should be viewed with caution since even well proven risk factors, such as the history of PONV, do not allow the identification of patients at risk for PONV with a satisfactory sensitivity or specificity. A more useful approach is the use of simplified risk scores which consider the presence of several risk factors simultaneously. Most individual antiemetic interventions for the prevention of PONV have comparable efficacy with a relative risk reduction of about 30%. This appears to be true for total intravenous anesthesia (TIVA) as well as for dexamethasone and other antiemetics; assuming a sufficiently high, adequate and equipotent dosage which should be weight-adjusted in children. As the relative risk reduction is context independent and similar between the interventions, the absolute risk reduction of prophylactic interventions is mainly dependent on the patient's individual baseline risk. Prophylaxis is thus rarely warranted in patients at low risk, generally needed in patients with a moderate risk and should include a multimodal approach in patients at high risk for PONV. Therapeutic interventions of PONV should be administered promptly using an antiemetic which has not been used before. The group suggests algorithms where prophylactic interventions are mainly dependent on the patient's risk for PONV. These algorithms should provide evidence-based guidelines allowing the development of SOPs/policies which take local circumstances into account.

Impaired insulin secretion in vivo but enhanced insulin secretion from isolated islets in pancreatic beta cell-specific vascular endothelial growth factor-A knock-out mice.

AIMS/HYPOTHESIS: Endothelial cells are considered to be essential for normal pancreatic beta cell function. However, there have been no reports showing their importance for beta cell function. MATERIALS AND METHODS: Using mice with disrupted vascular endothelial growth factor-A gene specifically in beta cells, we investigated the relation between islet vascular structure and beta cell function. RESULTS: Mice with disrupted vascular endothelial growth factor-A gene specifically in beta cells had reduced islet vascular density with impaired formation of endothelial fenestration. While their fasting glucose and body weight were comparable with control mice, their glucose- and tolbutamide-induced rapid insulin release were impaired, thus resulting in glucose intolerance. On the other hand, glucose and KCl enhanced the levels of insulin secreted from islets isolated from these mice. In addition, the production of soluble N-ethylmaleimide-sensitive factor attachment protein receptors in the islets was increased. Insulin content and expression of insulin I and pancreas duodenum homeobox 1 mRNA in the islets were also increased. CONCLUSIONS/INTERPRETATION: Our results indicate that an abnormal quality and quantity of blood vessels due to reduced expression of vascular endothelial growth factor-A in beta cells could be a cause of impaired insulin secretion without impairment of beta cell function.

Double-stranded secondary structures on mRNA induce type I interferon (IFN alpha/beta) production and maturation of mRNA-transfected monocyte-derived dendritic cells.

BACKGROUND: The development of dendritic cell (DC)-based vaccines using antigen-encoding mRNA requires identification of the critical parameters for efficient ex vivo loading of DCs. Exogenously delivered mRNA can induce DC activation, but the molecular mechanisms involved are unknown. The aim of the present study was to identify the means by which mRNA-dependent activation of DCs occurs. METHODS: In vitro transcribed mRNA molecules were delivered into porcine monocyte-derived DCs (MoDCs) using different non-viral gene transfer procedures. Using the green fluorescent protein (GFP) as reporter gene, as well as rhodamine-labeled RNA, intracellular delivery and transfection efficiency were assessed by confocal microscopy and flow cytometry. DC activation was monitored in terms of MHC class II and CD80/86 upregulation, as well as the production of type I interferon (IFN-alpha/beta). RESULTS: mRNA-lipofected MoDCs produced type I IFN and upregulated MHC class II and CD80/86. Computational analysis of the mRNA molecules predicted highly ordered secondary structures forming double-stranded RNA (dsRNA). This dsRNA was also detectable by immunofluorescence in mRNA-lipofected cells, using antibody specific for dsRNA. Digestion of the mRNA prior to lipofection with a double-strand-specific RNase, but not a single-strand-specific RNase, abrogated DC activation. Impairment of protein kinase R (PKR) with 2-aminopurine also interfered with the activation. CONCLUSIONS: Double-stranded secondary structures on mRNA delivered by lipofection can activate MoDCs. This could have important implications for mRNA-based immunomodulation of DCs, DC-based immunotherapy, and formulation of RNA-based vaccines. In addition, this report describes the first in vitro steps towards development of a novel large animal model system to evaluate DC-based vaccines against infectious diseases.

[The role of interventional pain therapy in palliative care]. / Was kann die interventionelle Schmerztherapie bieten?

The effective treatment of severe pain requires a multimodal approach with a thorough knowledge of the pharmacological properties of the individual drugs. Non-opioid analgesics are surprisingly effective and compare well to opioids. Due to the pain-induced changes in the spinal cord, the resulting tolerance and the specific effect of tumor mediators on the pain process, an effective treatment strategy requires in 10-30% of the tumor patients in the last weeks of their life an interventional approach to pain management. The common techniques involve neuroaxial delivery of local anaesthetics and opioids. There has been an abundant experience with these techniques in the perioperative setting. The indications are uncontrollable pain states and/or severe side effects of pain therapy including the cognitive deterioration with high dose opioids. The complications are mainly technical and are mostly due to catheter obstruction or disconnection. The increasing use of elastomeric pumps reduces the weight of the reservoir and allows the patient an easy adjustment of the flow rate.

Pilot study of urinary iodine concentration and of biochemical thyroid parameters before and after cautious public health intervention on salt iodide content: the Swiss longitudinal 1996-2000 iodine study.

OBJECTIVE AND DESIGN: Iodide concentration (IC) in salt was cautiously increased in Switzerland (15 --> 20 ppm iodide). We evaluated the dynamics of the effect of this intervention on urinary iodine concentration (UIC, microg/l) and on thyroid parameters. SETTING: University Hospital in Bern, Switzerland. SUBJECTS: A cohort of 36 subjects (12 children, 11 women, 13 men) out of 44 were recruited. INTERVENTIONS: During the study periods PRE (May 1996-May 1998) and POST (October 1998-December 2000, subdivided into equal subperiods POST1 and POST2), that is, before and after the increase of IC in salt, subjects collected 6248 urine spots for analysis of UIC. Thyroid volumes (n=2/subject) and serum thyroid parameters (n=8/subject) were sequentially evaluated. METHODS: Average PRE-POST data were compared (multiple regression analysis). RESULTS: UIC increased overall by 5.1% (P=0.0003). Increase of UIC was highest in children (11.3%, P<0.0001), significant in women (8%, P=0.0016), but not significant in men (P=0.143). Comparison between periods POST1 and POST2 showed that UIC changed more gradually in women than in children. Thyroid volumes were normal, no nonphysiological change occurred. TSH indicated euthyroidism; it decreased in children (1.98 ==> 1.74 mU/l, P=0.04) and increased in men (1.65 ==> 1.91mU/l, P=0.025). FT3 decreased in children (P<0.004) and FT4 decreased in men (P=0.017), both within normal ranges. TSH, FT3 and FT4 were unchanged in women. FT3/FT4 ratios were stable. Anti-TPO-Ab titers were stable (P=0.9). Anti-Tg-Ab titers decreased (P=0.009). CONCLUSION: The significant UIC effects were of uncertain metabolic relevance. No pathological side effects occurred. Differential delays and penetrances of UIC increase in children and adults were hitherto unknown. The unspectacular stepwise policy seems to be safe. Our pilot results in a population with moderate iodine deficiency in women should be confirmed in population-based cluster studies. SPONSORSHIP: This work was supported by grants from the University Hospital in Bern, the Swiss Federal Office of Public Health (SFOPH), the 'Swiss National Foundation for Scientific Research' (32-49424.96), the 'Fondation Genevoise de Bienfaisance Valerie Rossi di Montelera', the 'Schweizerische Lebensversicherungs- und Rentenanstalt' and the 'Schüpbach Foundation of the University of Bern'.

Quantification of urinary iodine: a need for revised thresholds.

OBJECTIVE: To compare different possibilities of reporting the iodine supply in the same urine samples. Indeed, in field studies, urinary iodine concentration (I/L: micro g I/L, micro mol I/L, I/creatinine: micro g I/g creatanine, micro mol I/mol creatinine) is more readily available than excretion (I/24h micro g I/24 h, micro mol I/24h). However, confusion exists regarding the comparability of iodine supply based upon I/L, I/creatinine and I/24h, which for decades have been regarded as biochemically equivalent. DESIGN: We compared I/24h, I/L and I/creatinine in accurate 24 h collections of urine and I/L and I/creatinine in 47 spot urine samples. PATIENTS: A total of 13 subjects (Bern n=7, Brussels n=6) collected a total of 110 precise 24 h urine collections (Bern n=63, Brussels n=47). The subjects from Brussels also took a spot sample at the beginning of each 24 h collection. RESULTS: Iodine supply in both places was mildly deficient according to the criteria of WHO; all but one collection indicated an intake of >0.39 micro mol I/24h (>50 micro g I/24h). The same data presented as I/creatinine (or I/L) indicated an iodine intake of <0.39 (<50 micro g I/24h) in 5% (24%) of the samples in Bern and 23% (57%) in Brussels. Similar findings were observed for 47 spot samples. Whatever the cut-off selected, I/creatinine and I/L were systematically lower than I/24h (P<0.0002). Creatinine showed smaller CV than volume but did not perform better in defining iodine intake. CONCLUSION: Considering I/24h as a reference, both I/creatinine and I/L clearly underestimate the iodine intake in subjects with adequate proteoenergetic intake. The significant deviations observed illustrate the urgent need for establishing separate ranges for I/24h, I/creatinine and I/L. In population studies, these deviations might even be larger.