Evaluation of degenerative disease of the lumbar spine: MR/MR myelography versus conventional myelography/post-myelography CT.

BACKGROUND: To compare the use of magnetic resonance (MR)/MR myelography (MRM) with conventional myelography/post-myelography CT (convM) for detailed surgery planning in degenerative lumbar disease. METHODS: Twenty-six patients with suspected complex lumbar degenerative disease underwent MRM in addition to convM as preoperative workup. Surgery was planned based on convM-as usual at our department. Post hoc, surgical planning was repeated planned again-now based on MRM. Furthermore, the MRM-based planning was performed by six independent neurosurgeons (three groups) of different degrees of specialisation. RESULTS: In only 31 % of the patients, post hoc MRM-based planning resulted in the same surgical decision as originally performed, whereas in 69 % (n = 18) a different procedure was indicated. In patients with non-concurring convM- and MRM-based surgical plans, a less extended procedure was the result of MRM in six patients (23 %), a more extended one in five (19 %), and a related to side/level of decompression or nucleotomy different plan in six patients (23 %). In one patient (4 %), the MRM-based planning would have led to a completely different surgery compared to convM. Overall interobserver agreement on the MRM-based planning was substantial. CONCLUSIONS: Detailed planning of operative procedures for complex lumbar degenerative disease is highly dependent on the image modality used.

Depicting adoptive immunotherapy for prostate cancer in an animal model with magnetic resonance imaging.

Genetically modified natural killer (NK) cells that recognize tumor-associated surface antigens have recently shown promise as a novel approach for cancer immunotherapy. To determine NK cell therapy response early, a real-time, noninvasive method to quantify NK cell homing to the tumor is desirable. The purpose of this study was to evaluate if MR imaging could provide a noninvasive, in vivo diagnosis of NK cell accumulation in epithelial cell adhesion molecule (EpCAM)-positive prostate cancers in a rat xenograft model. Genetically engineered NK-92-scFv(MOC31)-ζ cells, which express a chimeric antigen receptor specific to the tumor-associated EpCAM antigen, and nontargeted NK-92 cells were labeled with superparamagnetic particles of iron-oxides (SPIO) ferumoxides. Twelve athymic rats with implanted EpCAM positive DU145 prostate cancers received intravenous injections of 1.5×10(7) SPIO labeled NK-92 and NK-92-scFv(MOC31)-ζ cells. EpCAM-positive prostate cancers demonstrated a progressive and a significant decline in contrast-to-noise-ratio data at 1 and 24 h after injection of SPIO-labeled NK-92-scFv(MOC31)-ζ cells. Conversely, tumor contrast-to-noise-ratio data did not change significantly after injection of SPIO-labeled parental NK-92 cells. Histopathology confirmed an accumulation of the genetically engineered NK-92-scFv(MOC31)-ζ cells in prostate cancers. Thus, the presence or absence of a tumor accumulation of therapeutic NK cells can be monitored with cellular MR imaging. EpCAM-directed, SPIO labeled NK-92-scFv(MOC31)-ζ cells accumulate in EpCAM-positive prostate cancers.

A novel tool for objective assessment of femorotibial rotation: a cadaver study.

Traumatic rupture of the anterior cruciate ligament (ACL) of the knee is one of the most frequent orthopaedic sports' injuries. However, the best operative reconstruction technique is still the focus of current discussions among experts. While single-bundle reconstruction primarily addresses anterior-posterior instability, the anatomical double-bundle reconstruction aims to stabilise anterior-posterior as well as rotational instability. So far no definite evidence to favour the one or the other technique exists due to the lack of an objective method for quantifying rotational knee stability. In this context several authors have recently reported on devices for the analysis of femorotibial rotation. However, most of these tools are still in the developmental stage. Therefore, the aim of this study was (1) to develop a new instrument for assessing rotational knee stability independent from the surrounding soft tissue with an adequate method of analysis and (2) to establish the possible field of application of this device in a human cadaver study. The so-called torsiometer evaluated was designed to assess internal and external knee joint rotation objectively in different flexion angles. Measurements were performed implying internal and external rotation at 90°, 30° and 0° knee flexion with and without intact ACL, respectively. Each measurement revealed valid and reproducible values. The restraint in ACL-absent knees was clearly lower and the course of rotation explicitly higher than in knee joints with intact ACL.

Homozygosity of BACHD rats not only causes strong behavioral deficits in young female rats but also a reduced breeding success.

Huntington's disease is known to be a purely genetic disease based on an expansion of a CAG base triplet repeat in the coding region of the Huntingtin gene. Some years ago, researchers were able to introduce the extensive full-length gene sequence of the mutant huntingtin gene into a rodent model. The resulting BACHD rat is already well characterized for behavioral deficits. So far, all analyses in this preclinical rat model were performed in male hemizygous animals. As homozygosity of transgenic models often causes an amplification of the phenotype and female HD patients present a stronger phenotype compared to men, we established a homozygous breeding colony and tested 2 and 5 months old homozygous male and female BACHD rats in a behavioral test battery. The tests included the grip strength test, Rota Rod, elevated plus maze, passive avoidance, and Barnes maze test. Our results show strong deficits in young female homozygous BACHD rats including increased body weight, motor deficits, muscle weakness, reduced anxiety and hypoactivity, as well as learning and memory deficits. Analysis of male homozygous BACHD rats showed only weak disease symptoms, similar compared to male hemizygous BACHD rats of already published studies. Evaluation of the breeding success showed that homozygous BACHD have a reduced number of pups at the time of birth that even decreases until weaning. Our results suggest that the phenotype of homozygous male BACHD rats barely differs from already published results of hemizygous BACHD rats while female homozygous BACHD rats display strong and early alterations.

Real-Time PCR for Molecular Detection of Zoonotic and Non-Zoonotic Giardia spp. in Wild Rodents.

Giardiasis in humans is a gastrointestinal disease transmitted by the potentially zoonotic Giardia duodenalis genotypes (assemblages) A and B. Small wild rodents such as mice and voles are discussed as potential reservoirs for G. duodenalis but are predominantly populated by the two rodent species Giardia microti and Giardia muris. Currently, the detection of zoonotic and non-zoonotic Giardia species and genotypes in these animals relies on cumbersome PCR and sequencing approaches of genetic marker genes. This hampers the risk assessment of potential zoonotic Giardia transmissions by these animals. Here, we provide a workflow based on newly developed real-time PCR schemes targeting the small ribosomal RNA multi-copy gene locus to distinguish G. muris, G. microti and G. duodenalis infections. For the identification of potentially zoonotic G. duodenalis assemblage types A and B, an established protocol targeting the single-copy gene 4E1-HP was used. The assays were specific for the distinct Giardia species or genotypes and revealed an analytical sensitivity of approximately one or below genome equivalent for the multi-copy gene and of about 10 genome equivalents for the single-copy gene. Retesting a biobank of small rodent samples confirmed the specificity. It further identified the underlying Giardia species in four out of 11 samples that could not be typed before by PCR and sequencing. The newly developed workflow has the potential to facilitate the detection of potentially zoonotic and non-zoonotic Giardia species in wild rodents.

Suitability of current typing procedures to identify epidemiologically linked human Giardia duodenalis isolates.

BACKGROUND: Giardia duodenalis is a leading cause of gastroenteritis worldwide. Humans are mainly infected by two different subtypes, i.e., assemblage A and B. Genotyping is hampered by allelic sequence heterozygosity (ASH) mainly in assemblage B, and by occurrence of mixed infections. Here we assessed the suitability of current genotyping protocols of G. duodenalis for epidemiological applications such as molecular tracing of transmission chains. METHODOLOGY/PRINCIPAL FINDINGS: Two G. duodenalis isolate collections, from an outpatient tropical medicine clinic and from several primary care laboratories, were characterized by assemblage-specific qPCR (TIF, CATH gene loci) and a common multi locus sequence typing (MLST; TPI, BG, GDH gene loci). Assemblage A isolates were further typed at additional loci (HCMP22547, CID1, RHP26, HCMP6372, DIS3, NEK15411). Of 175/202 (86.6%) patients the G. duodenalis assemblage could be identified: Assemblages A 25/175 (14.3%), B 115/175 (65.7%) and A+B mixed 35/175 (20.0%). By incorporating allelic sequence heterozygosity in the analysis, the three marker MLST correctly identified 6/9 (66,7%) and 4/5 (80.0%) consecutive samples from chronic assemblage B infections in the two collections, respectively, and identified a cluster of five independent patients carrying assemblage B parasites of identical MLST type. Extended MLST for assemblage A altogether identified 5/6 (83,3%) consecutive samples from chronic assemblage A infections and 15 novel genotypes. Based on the observed A+B mixed infections it is estimated that only 75% and 50% of assemblage A or B only cases represent single strain infections, respectively. We demonstrate that typing results are consistent with this prediction. CONCLUSIONS/SIGNIFICANCE: Typing of assemblage A and B isolates with resolution for epidemiological applications is possible but requires separate genotyping protocols. The high frequency of multiple infections and their impact on typing results are findings with immediate consequences for result interpretation in this field.

Inter- and intraobserver variability of MR arthrography in the detection and classification of superior labral anterior posterior (SLAP) lesions: evaluation in 78 cases with arthroscopic correlation.

PURPOSE: The purpose of this study was to determine inter- and intraobserver variability of MR arthrography of the shoulder in the detection and classification of superior labral anterior posterior (SLAP) lesions. METHODS: MR arthrograms of 78 patients who underwent MR arthrography before arthroscopy were retrospectively analysed by three blinded readers for the presence and type of SLAP lesions. MR arthrograms were reviewed twice by each reader with a time interval of 4 months between the two readings. Inter- and intraobserver agreement for detection and classification of SLAP lesions were calculated using kappa coefficients. RESULTS: Arthroscopy confirmed 48 SLAP lesions: type I (n = 4), type II (n = 37), type III (n = 3), type IV (n = 4). Sensitivity and specificity for detecting SLAP lesions with MR arthrography for each reader were 88.6%/93.3%, 90.9%/80.0% and 86.4%/76.7%. MR arthrographic and arthroscopic grading were concurrent for 72.7%, 68.2% and 70.5% of SLAP lesions for readers 1-3, respectively. Interobserver agreement was excellent (kappa = 0.82) for detection and substantial (kappa = 0.63) for classification of SLAP lesions. For each reader intraobserver agreement was excellent for detection (kappa = 0.93, kappa = 0.97, kappa = 0.97) and classification (kappa = 0.94, kappa = 0.84, kappa = 0.93) of SLAP lesions. CONCLUSION: MR arthrography allows reliable and accurate detection of SLAP lesions. In addition, SLAP lesions can be diagnosed and classified with substantial to excellent inter- and intraobserver agreement.

Gustatory and olfactory function in breast cancer patients.

PURPOSE: Loss of appetite is a common complaint in cancer patients. There is still no overall conclusion whether this symptom might be caused by distorted taste/smell function or by tumor byproducts. This knowledge would be important for adequate patient counseling as well as symptom relief. Several studies investigated taste function, but to our knowledge, only one studied olfactory function in cancer patients. MATERIALS AND METHODS: Sixty-nine breast cancer patients were investigated by a validated taste (taste strips) and smell test (Sniffin' Sticks) prior to chemotherapy. RESULTS: Compared to normative data, breast cancer patients showed no significant difference in odor threshold, but better scores for odor identification and odor discrimination. For taste, breast cancer patients showed a significantly lower value for the quality sour compared to healthy controls only on left side of the tongue; there was no difference in the qualities sweet, salty, and bitter. An increase in tumor size was associated with a significant decrease in olfactory function, but not in gustatory function. Different histology or graduation of breast cancer, resection status, or metastasis to the lung and liver had no influence on taste and smell. There was no correlation between taste and smell to estrogen or progesterone receptor status. There was no correlation between smell and human epidermal growth factor receptor 2 (Her2 status), but there was a significant correlation between bitter taste and Her2 status. CONCLUSION: Taste/smell did not seem substantially altered in breast cancer patients compared to normative data. Nevertheless, increasing tumor burden resulted in decreased olfactory function, but not in taste changes.

Olfactory and gustatory function in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is the most common, functional disorder diagnosed by gastroenterologists. It is still unclear whether IBS has a central etiology, e.g., hyperreactivity of the brain, or a peripheral etiology, e.g., stimulation of olfactory/gustatory receptors on enterochromaffin cells, followed by serotonin release and changed gut motility. Testing the odor identification (ID), odor discrimination (DIS) and odor threshold (THR) as well as the total taste and the taste qualities "sweet", "sour", "salty" and "bitter" should be of help for determining the etiology. To our knowledge, this is the first study investigating the olfactory/gustatory function in IBS patients. The olfactory/gustatory function of 43 patients (32 women, 11 men) suffering from IBS as defined by the ROME III criteria was investigated by means of validated tests (Sniffin' Sticks and taste strips). Compared to normative data, scores of THR were decreased and scores of ID and DIS were increased in IBS patients. Additionally, when compared to normative data, there was no difference in the taste function of IBS patients. Assuming that THR reflects more the peripheral olfactory function, whereas ID and DIS are influenced by central activity, and that taste did not differ in IBS patients compared to normative data, this supports the idea of a central etiology of IBS.

Biomechanical in vitro validation of intramedullary cortical button fixation for distal biceps tendon repair: a new technique.

BACKGROUND: Extramedullary cortical button-based fixation for distal biceps tendon ruptures exhibits maximum load to failure in vitro but cannot restore the anatomic footprint and has the potential risk for injury to the posterior interosseous nerve. HYPOTHESIS: Double intramedullary cortical button fixation repair provides superior fixation strength to the bone when compared with single extramedullary cortical button-based repair. STUDY DESIGN: Controlled laboratory study. METHODS: The technique of intramedullary cortical button fixation with 1 or 2 buttons was compared with single extramedullary cortical button-based repair using 12 paired human cadaveric elbows. All specimens underwent computed tomography analysis to determine intramedullary dimensions of the radial tuberosity as well as the thickness of the anterior and posterior cortices before biomechanical testing. Maximum load to failure and failure modes were recorded. For baseline measurements, the native tendon was tested for maximum load to failure. RESULTS: The intramedullary area of the radial tuberosity provides sufficient space for single or double intramedullary cortical button implantation. The mean thickness of the anterior cortex was 1.13 ± 0.15 mm, and for the posterior cortex it was 1.97 ± 0.48 mm (P < .001). We found the highest loads to failure for double intramedullary cortical button fixation with a mean load to failure of 455 ± 103 N, versus 275 ± 44 N for single intramedullary cortical button fixation (P < .001) and 305 ± 27 N for single extramedullary cortical button-based technique (P = .003). There were no statistically significant differences between single intramedullary and single extramedullary button fixation repair (P = .081). The mean load to failure for the native tendon was 379 ± 87 N. CONCLUSION: Double intramedullary cortical button fixation provides the highest load to failure in the specimens tested. CLINICAL RELEVANCE: Double intramedullary cortical button fixation provides reliable fixation strength to the bone for distal biceps tendon repair and potentially minimizes the risk of posterior interosseous nerve injury. Further, based on a 2-point-fixation, this method may offer a wider, more anatomic restoration of the distal biceps tendon to its anatomic footprint.

Characterization of small (≤10 mm) focal liver lesions: value of respiratory-triggered echo-planar diffusion-weighted MR imaging.

PURPOSE: To evaluate respiratory-triggered diffusion-weighted MR imaging (DWI) in the characterization of small (≤10 mm) focal liver lesions (FLL). MATERIALS AND METHODS: A total of 185 FLL (76 metastases, 11 HCCs, 71 cysts, 18 hemangiomas, 6 focal nodular hyperplasias, 3 adenomas) were retrospectively analyzed in 77 patients. DWI was performed at 1.5 T using a respiratory-triggered single-shot echo-planar imaging (SSEPI) sequence (b values: 50, 300, 600 s/mm(2)). Diffusion-weighted images were evaluated by two independent observers and apparent diffusion coefficient (ADC) values were determined. Reference standard of diagnosis was obtained by two other radiologists correlating DWI with histopathologic findings, standard MR sequences and imaging follow-up. Receiver operating characteristic curve analysis was performed to evaluate the utility of ADC values for the diagnosis of malignancy. RESULTS: Accuracy for characterizing FLL was 93.0% for reader 1 and 91.9% for reader 2. Interobserver agreement was excellent between both readers (κ=0.88). Sensitivity and specificity for diagnosing malignancy were 90.8% and 89.9% using a threshold ADC of 1.41×10(-3) mm(2)/s. CONCLUSION: DWI using the respiratory-triggered SSEPI sequence can help to characterize FLL, even when the diameter of lesions is 10mm or less.

Taste in mild cognitive impairment and Alzheimer's disease.

In this prospective study we investigated the quantitative and qualitative taste function of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). 29 healthy, elderly subjects, 29 MCI and 30 AD patients were tested using a validated taste test, the "taste strips". Additionally, odor identification, odor discrimination, odor threshold, the mini-mental state examination (MMSE) and Apo E epsilon 4 status were examined. Regarding taste, there was a significant reduction of total taste scores and also the score for individual tastes on either side of the tongue between controls and MCI/AD patients. There was no significant difference in the taste scores between MCI and AD patients. A taste test may be a useful procedure for differentiating between healthy subjects and patients with MCI/AD in a clinical context. For diagnosing MCI versus AD, further tests such as smell test, MMSE, Apo E epsilon 4 status, FDG-PET and MRI appear to be useful.

Qualitative and quantitative assessment of taste and smell changes in patients undergoing chemotherapy for breast cancer or gynecologic malignancies.

PURPOSE: Smell and taste changes during chemotherapy are significant complaints of cancer patients. Loss of olfactory/gustatory function can lead to malnutrition, weight loss, and possibly a prolonged morbidity of chemotherapy-induced adverse effects, decreased quality of life, poor compliance, and even decreased therapy response. This prospective study comprehensively investigated, to our knowledge for the first time, smell and taste changes in a cohort of 87 patients undergoing chemotherapy for breast cancer or gynecologic malignancies. PATIENTS AND METHODS: Olfactory function was tested using Sniffin' Sticks (Burghart; Wedel, Germany) and gustatory function was tested using taste strips before, during, and immediately and 3 months after chemotherapy. RESULTS: Olfactory and gustatory function significantly decreased during chemotherapy and recovered almost completely 3 months after chemotherapy. Scores of odor thresholds were affected more than those of discrimination or identification. The olfactory function of older patients was affected more than that of younger patients. There was no difference in the olfactory function during chemotherapy with respect to the chemotherapeutic agent or initial diagnosis (breast or ovarian cancer). Regarding taste, scores of salty taste were affected more than scores of sweet, sour, or bitter taste. The gustatory function did not differ significantly during chemotherapy with respect to age or diagnosis but did differ with respect to the chemotherapeutic agent. Taxane-based chemotherapy caused the most severe disorders. CONCLUSION: Chemotherapy has a significant but transient effect on olfactory and gustatory function, possibly causing reduced appetite, a low energy intake, and weight loss. Additional spices and flavoring may compensate for this diminished chemosensory function, enhancing patient compliance and quality of life.