MR-Guided Percutaneous Intradiscal Thermotherapy (MRgPIT): Evaluation of a New Technique for the Treatment of Degenerative Disc Disease in Cadaveric Lumbar Spine.

PURPOSE: Evaluation of MR feasibility and real-time control of an innovative thermoablative applicator for intradiscal thermotherapy and histological analysis of laser annuloplasty in human ex vivo intervertebral discs. MATERIALS AND METHODS: We evaluated a new MR-compatible applicator system for MR-guided percutaneous intradiscal thermotherapy (MRgPIT) in an open 1.0-T MRI-system. Needle artefacts and contrast-to-noise ratios (CNR) of six interactive sequences (PD-, T1-, T2w TSE, T1-, T2w GRE, bSSFP) with varying echo-times (TE) and needle orientations to the main magnetic field (B0) were analysed. Additionally, five laser protocols (Nd: YAG Laser, 2-6 W) were assessed in 50 ex vivo human intervertebral discs with subsequent histological evaluation. RESULTS: In vitro, we found optimal needle artefacts of 1.5-5 mm for the PDw TSE sequence in all angles of the applicator system to B0. A TE of 20 ms yielded the best CNR. Ex vivo, ablating with 5 W induced histological denaturation of collagen at the dorsal annulus, correlating with a rise in temperature to at least 60 °C. The MRgPIT procedure was feasible with an average intervention time of 17.1 ± 5.7 min. CONCLUSION: Real-time MR-guided positioning of the MRgPIT-applicator in cadaveric intervertebral disc is feasible and precise using fast TSE sequence designs. Laser-induced denaturation of collagen in the dorsal annulus fibrosus proved to be accurate.

Pathogenesis and treatment of HIV infection: the cellular, the immune system and the neuroendocrine systems perspective.

Infections with HIV represent a great challenge for the development of strategies for an effective cure. The spectrum of diseases associated with HIV ranges from opportunistic infections and cancers to systemic physiological disorders like encephalopathy and neurocognitive impairment. A major progress in controlling HIV infection has been achieved by highly active antiretroviral therapy (HAART). However, HAART does neither eliminate the virus reservoirs in form of latently infected cells nor does it completely reconstitute immune reactivity and physiological status. Furthermore, the failure of the STEP vaccine trial and the only marginal efficacies of the RV144 trial together suggest that the causal relationships between the complex sets of viral and immunological processes that contribute to protection or disease pathogenesis are still poorly understood. Here, we provide an up-to-date overview of HIV-host interactions at the cellular, the immune system and the neuroendocrine systems level. Only by integrating this multi-level knowledge one will be able to handle the systems complexity and develop new methodologies of analysis and prediction for a functional restoration of the immune system and the health of the infected host.

Magnetic resonance imaging of the active second stage of labour: proof of principle.

OBJECTIVE: To prove that magnetic resonance imaging of foetal anatomy during the active second stage of vaginal delivery is feasible. MATERIALS AND METHODS: Initially, five pregnant volunteers around the 30th week of gestation were examined in an open MRI. Based on the findings, one vaginal delivery was acquired under real-time imaging. To monitor the birth status during image acquisition, an MR-compatible wireless cardiotocography (CTG) system was built. Single-shot sequence parameters were optimised to compensate motion artefacts during labour. RESULTS: Safety requirements to monitor the birth process under real-time MR imaging were met. High-resolution MR images were acquired immediately before and after delivery. In one patient, TSE single-shot cinematic sequences of the active second stage of labour were obtained. All sequences were adapted to tolerate movement of the mother and infant, as well as residual noise from the CTG. Furthermore, the MR imaging during labour showed only minor image artefacts. CONCLUSION: CTG-monitored acquisition of MRI series during the active second stage of delivery is feasible. Image quality should allow various further studies to improve models for birth simulation as well as potential investigation of obstructed labour and obstetric complications.

[A wireless communication system for interventional MRI]. / Ein kabelloses Kommunikationssystem für die interventionelle MRT.

The available MR-compatible communication systems, which are typically designed for diagnostic exams, are mostly based on tubular sound transmission. In other settings, modern commercially available communication systems with ear protection allow wireless communication in noisy environments. The application of MR-compatible wireless headsets in interventional radiology precludes tube contact with sterile surfaces and hindrance of the interventionalist's range of motion. The system introduced here allows wireless communication within the scanner room without influencing MR image quality.

[Conception and course of eight pregnancies in five women on TNF blocker etanercept treatment]. / Konzeption und Verlauf von acht Schwangerschaften bei fünf Patientinnen unter TNF-α-Blockade mit Etanercept.

The introduction of tumor necrosis factor (TNF)-α inhibitors s in the late 1990s considerably broadened the treatment options for, and essentially contributed to the successful management of, rheumatoid arthritis (RA) and other immune-mediated inflammatory diseases. Nevertheless, their use during pregnancy is still controversially discussed since it remains unclear whether the benefits of treatment might be outweighed by potential teratogenicity or adverse effects on the course of pregnancy. In this case series report we describe the course and outcome of eight pregnancies in five women (four with RA and one with ankylosing spondylitis) at our private clinical practice treated with the TNF-α inhibitor etanercept at the time of conception and during pregnancy. The course was inconspicuous in six of the eight pregnancies; in one case a megacolon congenitum was diagnosed 2 weeks after birth, while one spontaneous abortion occurred in the 10th week of pregnancy after a disease flare following treatment discontinuation with etanercept in the 5th week of pregnancy. Based on our experience to date and the currently available literature data, we believe that continuation of treatment with TNF-α blockers is justified in pregnant patients with otherwise high disease activity and disease progression.

Laser-induced thermotherapy (LITT)--evaluation of a miniaturised applicator and implementation in a 1.0-T high-field open MRI applying a porcine liver model.

OBJECTIVE: To evaluate the feasibility and safety of a novel LITT applicator for thermal ablation of liver malignancies in 1.0-T high-field open MRI. METHODS: A miniaturised 6-F double-tubed protective catheter with a closed cooling circuit was used with a flexible laser fibre, connected to a 1,064-nm Nd:YAG laser and evaluated in non-perfused porcine livers (18-30 W for 10-20 min, 2-W and 2-min increments; n = 210/applicator) in reference to an established 9-F system. As a proof of concept, MR-guided LITT was performed in two healthy domestic pigs in high-field open MRI. RESULTS: Ex-vivo, the coagulation volumes induced by the 6-F system with maximum applicable power of 24 W for 20 min (33.0 ± 4.4 cm(3)) did not differ significantly from those set with the 9-F system at 30 W for 20 min (35.8 ± 4.9 cm(3)) (p = 0.73). A flow-rate of 15 ml/min of the cooling saline solution was sufficient. MR navigation and thermometry were feasible. CONCLUSION: The miniaturised 6-F applicator can create comparable coagulation sizes to those of the 9-F system. Applicator guidance and online-thermometry in high-field open MRI are feasible.

[Adaptation of a wireless PC mouse for modification of GUI during intervention in an open highfield MRI at 1.0T]. / Modifikation einer kabellosen PC-Maus fA(1/4)r die Steuerung der BedieneroberflA currencyche wA currencyhrend der Intervention in der offenen Hochfeld-MRT bei 1,0 T.

PURPOSE: To demagnetize a PC mouse for interventional use in magnetic resonance imaging (MRI). MATERIALS AND METHODS: A mobile version of a wireless optical mouse at 2.470 Hz was modified in ways ranging from the replacement of magnetic components to the construction of new components. The magnetic force (Fm), the induction of susceptibility artifacts, and the signal-to-noise ratio (SNR) were determined. The modified mice at 1.0 T. were used in MR-guided interventions. RESULTS: A final demagnetization down to 2 % (Fm = 9 N vs. Fm = 0.15 N) was achieved. Operating the device clinically caused no compromise in image quality. From a minimal distance of about 20 cm, even the non-modified mouse did not produce any susceptibility artifacts in gradient recalled imaging. The SNR was not reduced significantly (TSE 228 + or - 22,3 vs. 211 + or - 15; FFE 55 + or - 5,6 vs. 56 + or - 4,3). For over a year the modified mouse proved to be a reliable tool for the interventionalist to manipulate MRI. CONCLUSION: Relatively inexpensive modifications of a standard USB mouse enable the interventionalist to work independently without a technical assistant and to take immediate advantage of multiplanar MR imaging during interventions.

Imaging sequences for intraoperative MR-guided laparoscopic liver resection in 1.0-T high field open MRI.

The aim of this study was to identify suitable interactive (dynamic) magnetic resonance (MR) sequences for real-time MR-guided liver dissection in a 1.0-T high field open MRI system. Four dynamic sequences encompassing balanced steady state free precession (bSSFP), T1W gradient echo (GRE), T2W GRE and T2W fast spin echo (FSE) were analysed regarding the image quality, artefact susceptibility and the performance of SNR and CNR. The T2W FSE sequence (1.5 s/image) was considered superior because of an intraoperative SNR of 6.9 (+/-0.7) and CNR (vessel to parenchyma) of 5.6 (+/-1.7) in the interventional setting. As a proof of concept, MR-guided laparoscopic liver resection was performed in two healthy domestic pigs by using the T2W FSE sequence. The additional MR images offered simultaneous multiplanar real-time visualisation of the liver vessels during the intervention and thereby increased the anatomical orientation of the surgeon.

MR-guided laser ablation of osteoid osteoma in an open high-field system (1.0 T).

Computed tomography is the standard imaging modality to minimize the extent of surgical or ablative treatment in osteoid osteomas. In the last 15 years, since a description of thermal ablation of osteoid osteomas was first published, this technique has become a treatment of choice for this tumor. We report the case of a 20-year-old man with an osteoid osteoma treated with laser ablation in an open high-field magnetic resonance imaging scanner (1.0 T). The tumor, located in the right fibula, was safely and effectively ablated under online monitoring. We describe the steps of this interventional procedure and discuss related innovative guidance and monitoring features and potential benefits compared with computed tomographic guidance.

Hepatotoxicity in patients prescribed efavirenz or nevirapine.

AIM: For several years Nonnucleoside reverse transciptase inhibitors (NNRTIs) in antiretroviral therapy have been associated with hepatic side effects. Particularly the hepatotoxic potential of Nevirapine is well analysed today. We performed a prospective, multicenter study to compare the hepatotoxicity of Efavirenz (EFV) with that of Nevirapine (NVP) and to investigate further risk factors. MATERIAL AND METHODS: The study included HIV-1-infected patients from five clinics and private medical practices in southwestern Germany who initiated an antiretroviral therapy with NVP or EFV between July 1998 and December 2001. Among 296 patients in total, 151 received EFV and 145 received NVP. Laboratory tests during the course of treatment included liver enzymes, HIV-RNA and CD4 cell-count. Additionally, signs of clinical hepatitis were recorded. Hepatotoxicity was graded in the manner of Sulkowsky et al. (2000), who used a scale modified from that of the AIDS Clinical Trials Group. RESULTS: Hepatitis C virus and hepatitis B virus were detected in 10.1% and 4.1% of patients, respectively. The overall rate of severe hepatotoxicity (grade 3 to 4 elevations in aspartate aminotransferase and/or alanine aminotransferase) was 2 of 151 (1.3%) in patients prescribed EFV and 3 of 145 (2.1%) in patients prescribed NVP. Mild-to-moderate hepatotoxicity (grade 2 elevation) was observed in 6.0% (EFV) and 3.4% (NVP) of patients. Incidence of mild-to-moderate and severe hepatotoxicity did not differ significantly between the study groups. 3 of 14 patients (2.1%) with grade 2 elevation of liver enzymes (LEE) and 4 of 5 patients (80%) with grade 3 to 4 LEE were symptomatic. Only risk factor for the development of mild-to-moderate hepatotoxicity was hepatitis C coinfection. CONCLUSION: Increases of liver enzymes during therapy with NVP or EFV are not unusual, but are mostly mild-to-moderate and asymptomatic. LEE occurs just as frequent in patients prescribed EFV as in patients prescribed NVP.

Is anterior release effective to increase flexibility in idiopathic thoracic scoliosis? Assessment by traction films.

With the advent of thoracoscopy, anterior release procedures in adolescent idiopathic scoliosis (AIS) have come into more frequent use, however, the indication criteria for an anterior release in thoracic AIS are still controversial in the literature. To date, few studies have assessed the influence on spinal flexibility and no study has so far been able to show a beneficial effect on the correction rate as compared to a single posterior procedure. The objective of this study was to evaluate the influence of thoracic disc excision on coronal spinal flexibility. Six patients (5 females, 1 male) with AIS and a mean age of 15.6 years (range 13-20 years) underwent an open anterior thoracic release prior to posterior instrumentation. Cotrel dynamic traction along with radiographs of the whole spine including traction films were conducted pre- and postoperatively and were evaluated retrospectively. The mean preoperative thoracic curve was 89.7 degrees +/- 15.4 degrees (range 65 degrees-110 degrees). The flexibility rate in Cotrel traction was 22.8 +/- 8.1%. After performance of the anterior release the thoracic curve showed a mean increase of coronal correction by 5.5 degrees +/- 5.0 degrees as assessed by traction radiographs. The flexibility index changed by 6.2 +/- 5.6%. After posterior instrumentation the thoracic curve was corrected to a mean of 36.5 degrees +/- 10.1 degrees (correction rate 59.6%). Disc excision in idiopathic thoracic scoliosis only slightly increased spinal flexibility as assessed by traction films. In our view a posterior release with osteotomy of the concave ribs (concave thoracoplasty, CTP) is more effective in increasing spinal flexibility. According to our clinical experience, an anterior release prior to posterior instrumentation in AIS should only be considered in hyperkyphosis, coronal imbalance or massive curves.

Three-dimensional analysis of shear wave propagation observed by in vivo magnetic resonance elastography of the brain.

Dynamic magnetic resonance elastography (MRE) is a non-invasive method for the quantitative determination of the mechanical properties of soft tissues in vivo. In MRE, shear waves are generated in the tissue and visualized using phase-sensitive MR imaging methods. The resulting two-dimensional (2-D) wave images can reveal in-plane elastic properties when possible geometrical biases of the wave patterns are taken into account. In this study, 3-D MRE experiments of in vivo human brain are analyzed to gain knowledge about the direction of wave propagation and to deduce in-plane elastic properties. The direction of wave propagation was determined using a new algorithm which identifies minimal wave velocities along rays from the surface into the brain. It was possible to quantify biases of the elastic parameters due to projections onto coronal, sagittal and transversal image planes in 2-D MRE. It was found that the in-plane shear modulus is increasingly overestimated when the image slice is displaced from narrow slabs of 2-5cm through the center of the brain. The mean shear modulus of the brain was deduced from 4-D wave data with about 3.5kPa. Using the proposed slice positions in 2-D MRE, this shear modulus can be reproduced with an acceptable error within a fraction of the full 3-D examination time.

[Rashes in HIV-infected patients undergoing therapy with nevirapine or efavirenz]. / Arzneimittelexantheme bei Therapie der HIV-Infektion mit Efavirenz und Nevirapin.

Efavirenz and nevirapine are frequently used drugs in antiretroviral therapy. Rashes are common side effects of these drugs. In this study, we examined the characteristics of efavirenz- and nevirapine-associated rashes. This prospective nonrandomized multicenter study included 662 HIV-infected patients (efavirenz: 325, nevirapine: 337) to determine incidence, duration, cross-reactivity, and outcome upon reexposure. Of the treated patients, 4.5% (n=30) developed rashes (nevirapine: 2.4% and efavirenz: 6.4%). In four patients treatment was not interrupted. Three patients were re-exposed to the initial drug without any side effects. Therapy with nevirapine or efavirenz does not have to be interrupted if rashes exhibit no blistering, mucosal manifestations, or systemic signs.

Prognostic value of proliferative responses to HIV-1 antigen in chronically HIV-infected patients under antiretroviral therapy.

BACKGROUND: In the chronic stage of HIV infection T cell proliferative responses to HIV antigens are rare, mostly of low level, and the influence of responses on antiretroviral therapy is not known. OBJECTIVES: To determine a potential correlation between HIV-specific proliferative responses and the subsequent course of infection under antiretroviral therapy. STUDY DESIGN: Proliferation assays were performed with freshly isolated blood mononuclear cells from 45 chronically HIV-infected HAART treated individuals using HIV-p24, other recall antigens, and mitogens as stimulants. Virus load was monitored at the time of stimulation and during 33 months follow-up. RESULTS: A proliferative response to HIV antigen stimulation was detectable in 7 of 45 patients (15.5% responders). This group showed elevated reactions against tetanus toxoid and tuberculin, whereas reactions against standard mitogens were equal in the HIV responder and nonresponder groups. None of the seven HIV-specific responders had a blood virus load rebound of more than 1000 genome copies/ml during follow-up, whereas in 50% of the non-responders higher virus rebounds occurred. CD4 cell levels were slightly higher in the responder group, but mostly independent of virus rebound within the non-responders. Only four patients with high and continuous virus rebound experienced a significant CD4 cell decline. CONCLUSIONS: In patients under HAART, HIV-specific proliferative response is frequently related to anamnestic antigen responses and an enduring control of virus replication.

Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation.

Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.

A double-blind, placebo-controlled, crossover therapy study with natural human IL-2 (nhuIL-2) in combination with regular intravenous gammaglobulin (IVIG) infusions in 10 patients with common variable immunodeficiency (CVID).

Ten CVID patients with defective IL-2 synthesis in vitro were treated with nhuIL-2 in a placebo-controlled, double blind, crossover therapy study during a period of 12 months. No severe side-effects of nhuIL-2 were recorded. Marginal serum nhuIL-2 levels were measurable in individual patients only during the therapy phase. Serum levels of soluble IL-2 receptors were unaffected by the therapy. nhuIL-2 and placebo groups did not differ significantly with respect to requirement of IVIG substitutions which were performed whenever serum IgG levels dropped below 5 g/l: a total of 53 IVIG infusions (corresponding to 17.6 g IgG/month per patient) was necessary during the placebo phase, and 48 infusions (16.4 g IgG/month per patient) during the nhuIL-2 treatment phase. Thus, nhuIL-2 therapy was ineffective in improving spontaneous IgG synthesis in vivo. Nevertheless, the group of patients receiving nhuIL-2 during the first 6 months of the study exhibited a significant reduction of severe infections (n = 25) during the following 6 months of placebo treatment (n = 7) (P<0.045). The infection score dropped in this group from 181 to 23 (P<0.015). Patients of the second group receiving first placebo and then nhuIL-2 did not experience a significant difference in number and score of infectious episodes: 25 infections were recorded during the first 6 months and 24 during the following 6 months. We suppose that nhuIL-2 therapy of CVID patients reduces susceptibility to severe infections, possibly via the induction of a specific antibody response, which is effective at the earliest 6 months after initiating nhuIL-2 therapy.

Isolation of Helicobacter pullorum from patients with enteritis.

Helicobacter pullorum, recently described as sp. nov., is commonly isolated from asymptomatic poultry. Two cases of human enteritis associated with H. pullorum, one of them in an immunocompromised patient, are reported. Problems in the correct species identification by means of phenotypic and genotypic methods are discussed and for the first time a fatty acid pattern of Helicobacter pullorum is presented.

Clinical utility of cytomegalovirus urine cultures for ophthalmic care in patients with HIV.

BACKGROUND: The utility of cytomegalovirus (CMV) urine cultures was checked in patients with HIV (a) to identify those at risk for CMV retinitis and (b) to guide clinical decisions on treatment and prophylaxis of CMV retinitis. METHODS: HIV infected patients were tested for CMVuria by shell vial cell cultures. The prevalence of CMVuria was related to CD4 count, HIV risk group, and time before and after diagnosis of CMV retinitis. RESULTS: A total of 639 shell vial cell cultures were obtained from 266 HIV infected ophthalmic patients. Only 4% of all patients with a CD4 count > 400 x 10(6)/l shed CMV in their urine compared with 42% with a CD4 count < or = 50 x 10(6)/l. Twenty three of 25 patients with CMV retinitis had a CD4 count < or = 50 x 10(6)/l. Among 130 patients with a CD4 count < or = 50 x 10(6)/l (a) those who were CMVuric had a nearly sevenfold risk (p < 0.0001) of developing CMV retinitis (35%) compared with those who did not shed CMV in their urine (5%), and (b) CMVuria and CMV retinitis were more frequent in homosexuals (58%/25%) than in intravenous drug users (23%/15%). More than 1 year before diagnosis of CMV retinitis 18% of patients were CMVuric compared with 83% of patients who were CMV culture positive in the last 3 months. CMVuria under virustatic maintenance therapy is associated with worsening of retinitis in two thirds of cases. CONCLUSION: Ophthalmic screening of patients with HIV should include those with a CD4 count < or = 50 x 10(6)/l and focus on the subgroup with additional CMVuria. Screening of other patients can be dropped without undue risk in order to spare AIDS patients unnecessary hospital visits. CMVuria as a single finding, however, does not justify antiviral prophylaxis of CMV retinitis.