Severe acute drug-induced dystonia in the post-operative period requiring tracheal re-intubation.

Ondansetron is a highly selective 5-hydroxytryptamine receptor antagonist and the most commonly used anti-emetic for the prevention of postoperative nausea and vomiting. Ondansetron has a low affinity for dopamine receptors and so extrapyramidal side effects are rare. Here, we present the case of a 14-year-old girl who developed a severe post-operative acute dystonic reaction which included oculogyric crisis. We believe that ondansetron was the most likely cause, although propofol may have been a synergistic or alternative causative agent. The patient had no significant past medical history and had previously undergone two uneventful general anaesthetics which included both ondansetron and propofol. The prolonged duration and severity of the reaction and failure to fully respond to specific treatments resulted in the need for tracheal intubation and transfer to a paediatric intensive care unit. She subsequently recovered uneventfully with no ongoing neurological sequalae. Ondansetron-induced dystonic reactions are rare and unpredictable and can occur in patients who have previously received the drug without complication. They are thought to be caused by an imbalance between inhibitory and excitatory neurotransmitters in the extrapyramidal system. Specific treatments include anticholinergics, antihistamines and benzodiazepines.

Imaging and the completion of the omics paradigm in breast cancer.

Within the field of oncology, "omics" strategies-genomics, transcriptomics, proteomics, metabolomics-have many potential applications and may significantly improve our understanding of the underlying processes of cancer development and progression. Omics strategies aim to develop meaningful imaging biomarkers for breast cancer (BC) by rapid assessment of large datasets with different biological information. In BC the paradigm of omics technologies has always favored the integration of multiple layers of omics data to achieve a complete portrait of BC. Advances in medical imaging technologies, image analysis, and the development of high-throughput methods that can extract and correlate multiple imaging parameters with "omics" data have ushered in a new direction in medical research. Radiogenomics is a novel omics strategy that aims to correlate imaging characteristics (i. e., the imaging phenotype) with underlying gene expression patterns, gene mutations, and other genome-related characteristics. Radiogenomics not only represents the evolution in the radiology-pathology correlation from the anatomical-histological level to the molecular level, but it is also a pivotal step in the omics paradigm in BC in order to fully characterize BC. Armed with modern analytical software tools, radiogenomics leads to new discoveries of quantitative and qualitative imaging biomarkers that offer hitherto unprecedented insights into the complex tumor biology and facilitate a deeper understanding of cancer development and progression. The field of radiogenomics in breast cancer is rapidly evolving, and results from previous studies are encouraging. It can be expected that radiogenomics will play an important role in the future and has the potential to revolutionize the diagnosis, treatment, and prognosis of BC patients. This article aims to give an overview of breast radiogenomics, its current role, future applications, and challenges.

Clinical role of breast MRI now and going forward.

Magnetic resonance imaging (MRI) is a well-established method in breast imaging, with manifold clinical applications, including the non-invasive differentiation between benign and malignant breast lesions, preoperative staging, detection of scar versus recurrence, implant assessment, and the evaluation of high-risk patients. At present, dynamic contrast-enhanced MRI is the most sensitive imaging technique for breast cancer diagnosis, and provides excellent morphological and to some extent also functional information. To compensate for the limited functional information, and to increase the specificity of MRI while preserving its sensitivity, additional functional parameters such as diffusion-weighted imaging and apparent diffusion coefficient mapping, and MR spectroscopic imaging have been investigated and implemented into the clinical routine. Several additional MRI parameters to capture breast cancer biology are still under investigation. MRI at high and ultra-high field strength and advances in hard- and software may also further improve this imaging technique. This article will review the current clinical role of breast MRI, including multiparametric MRI and abbreviated protocols, and provide an outlook on the future of this technique. In addition, the predictive and prognostic value of MRI as well as the evolving field of radiogenomics will be discussed.

The impact of bilateral salpingo-oophorectomy on breast MRI background parenchymal enhancement and fibroglandular tissue.

OBJECTIVE: The objective of this study was to evaluate the effect of bilateral salpingo-oophorectomy (BSO) on background parenchymal enhancement (BPE) and the amount of fibroglandular tissue (FGT) seen on breast MRI. METHODS: Retrospective review identified 21 BRCA mutation carriers who underwent breast MRI before and after elective BSO. After exclusion of patients placed on postoperative hormone replacement therapy, there were 18 eligible patients. Blinded to surgical status, three independent readers used categorical scales to rate BPE (minimal, mild, moderate, marked) and the amount of FGT (fatty, scattered, heterogeneously dense, dense) on pre- and post-BSO MRI examinations. The sign test was used to assess for changes in the categorical ratings of BPE and FGT. RESULTS: Significant proportions of women demonstrated decreases in BPE and in the amount of FGT following oophorectomy (P = 0.004 and 0.02, respectively.) BPE decreases were larger and seen earlier than FGT changes. There was no significant relationship between age/body mass index and changes in BPE and FGT. CONCLUSIONS: BPE and the amount of FGT seen on breast MRI are significantly decreased by oophorectomy; BPE decreases to a greater extent and earlier than FGT. KEY POINTS: • Background parenchymal enhancement significantly decreases at breast MRI following oophorectomy. • Fibroglandular tissue significantly decreases on breast MRI following oophorectomy. • Decrease in background parenchymal enhancement is greater than in fibroglandular tissue. • Decrease in background parenchymal enhancement occurs earlier than in fibroglandular tissue.

Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor.

OBJECTIVE: To evaluate aggrecanase activity after traumatic knee injury in a rat model by measuring the level of aggrecanase-generated Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments in synovial fluid, and compare with ARG-aggrecan release into joint fluid following human knee injury. To evaluate the effect of small molecule inhibitors on induced aggrecanase activity in the rat model. METHOD: An enzyme-linked immunosorbent assay (ELISA) was developed to measure ARG-aggrecan levels in animal and human joint fluids. A rat model of meniscal tear (MT)-induced joint instability was used to assess ARG-aggrecan release into joint fluid and the effects of aggrecanase inhibition. Synovial fluids were also obtained from patients with acute joint injury or osteoarthritis and assayed for ARG-aggrecan. RESULTS: Joint fluids from human patients after knee injury showed significantly enhanced levels of ARG-aggrecan compared to uninjured reference subjects. Similarly, synovial fluid ARG-aggrecan levels increased following surgically-induced joint instability in the rat MT model, which was significantly attenuated by orally dosing the animals with AGG-523, an aggrecanase specific inhibitor. CONCLUSIONS: Aggrecanase-generated aggrecan fragments were rapidly released into human and rat joint fluids after injury to the knee and remained elevated over a prolonged period. Our findings in human and preclinical models strengthen the connection between aggrecanase activity in joints and knee injury and disease. The ability of a small molecule aggrecanase inhibitor to reduce the release of aggrecanase-generated aggrecan fragments into rat joints suggests that pharmacologic inhibition of aggrecanase activity in humans may be an effective treatment for slowing cartilage degradation following joint injury.

The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse.

OBJECTIVE: To evaluate anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgical instability models of osteoarthritis (OA) in the 129/SvEv mouse knee joint. DESIGN: Micro-surgical techniques were used to perform ACLT or DMM under direct visualization. Histological scoring was performed on multiple sections to assess cartilage damage across the entire joint. RESULTS: The ACLT model gave severe OA, chondrogenesis of the joint capsule and, in some cases, severe subchondral erosion of the posterior tibial plateau. Surgical DMM was less invasive than the ACLT procedure and resulted in lesions primarily on the central weight-bearing region of the medial tibial plateau and medial femoral condyles. Lesions in the DMM model progressed from mild-to-moderate OA at 4 weeks, to moderate-to-severe OA at 8 weeks post-surgery. Destruction of the subchondral bone was never observed in the DMM model. CONCLUSIONS: ACLT is not recommended in the mouse due to the high surgical proficiency required and the development of severe OA that may involve subchondral bone erosion. The severity and location of lesions following DMM are consistent with lesions observed in aged spontaneous mouse models of OA. The DMM model has sufficient sensitivity to show disease modification, as observed with the ADAMTS-5 knock out (KO) mouse. The DMM model should be a first choice to challenge mice with gene deletions of potential targets in OA.

Osteoarthritis severity is sex dependent in a surgical mouse model.

OBJECTIVE: To investigate the role of sex hormones in cartilage degradation and progression of osteoarthritis (OA) in a murine model induced by destabilization of the medial meniscus (DMM). DESIGN: Accelerated OA development in mice was induced by transection of the menisco-tibial ligament, which anchors the medial meniscus to the tibial plateau. Intact male and female, and orchiectomized (ORX) male and ovariectomized (OVX) female mouse knee histology were compared for signs of OA following DMM. The effect of testosterone or estrogen addition in vivo was assessed in ORX males in the surgical OA model. RESULTS: OA severity was markedly higher in males than females after DMM. OVX females developed significantly more severe OA than control females. ORX males developed significantly less severe OA than control males. When ORX male mice were supplemented with exogenous dihydrotestosterone (DHT), the severity of OA was restored to the level experienced by the control male mice. Hip cartilage from mice of both sexes demonstrated similar spontaneous and interleukin-1alpha (IL-1alpha) induced proteoglycan (PG) release in vitro. DHT and 17-beta estradiol (E2) did not significantly alter the PG release pattern when supplemented to cartilage cultures of either sex. CONCLUSION: Sex hormones play a critical role in the progression of OA in the murine DMM surgical model, with males having more severe OA than females. Intact females had more OA than OVX females, indicating that ovarian hormones decrease the severity of OA in the female mice. Male hormones, such as testosterone, exacerbate OA in male mice as demonstrated by the fact that ORX mice experienced less OA than intact males, and that addition of DHT to ORX males was able to counteract the effect of castration and re-establish severe OA.

Checking the capnograph before anaesthesia: a survey of national practice in the UK.

BACKGROUND AND OBJECTIVE: Recently published guidelines for checking anaesthetic equipment do not contain specific advice on how to check the correct functioning of the capnograph before inducing anaesthesia. METHODS: We undertook a postal survey of UK consultant (physician) anaesthetists to establish what methods for checking the capnograph are currently in use. Two hundred and two questionnaires were sent to consultants in different hospitals and 163 returned, a response rate of 81%. RESULTS: 52.1% consultants of check the capnograph themselves. Of these, 55.3% use their own expired breath to confirm a response to carbon dioxide. Other methods used by consultant anaesthetists to check capnograph function include the machine self-test (16.5%), visual checks of the capnograph and sampling tubing (10.3%), and sampling of patient expired carbon dioxide (7.1%). CONCLUSION: The most common method for testing capnograph function among consultant anaesthetists and their assistants in the UK is the direct measurement of exhaled breath.

Magnetic resonance imaging detects unsuspected disease in patients with invasive lobular cancer.

BACKGROUND: Predicting the extent of disease in the breasts of patients with invasive lobular cancer (ILC) can be difficult because of the limits of physical examination and standard imaging. We determined the utility of magnetic resonance imaging (MRI) in finding otherwise unsuspected cancer in the ipsilateral or contralateral breast of patients with ILC. METHODS: Through database review of all breast MRIs performed between January 1, 1999, and December 30, 2002, we identified patients with newly diagnosed ILC who underwent an MRI for extent-of-disease evaluation or contralateral screening. MRI findings separate from the primary tumor were biopsied and correlated with pathology by using MRI-guided biopsy. RESULTS: Sixty-two patients were identified. In all, 59 ipsilateral and 57 contralateral studies were performed. Suspicious lesions separate from the primary tumor were found by MRI in 38 (61%) of 62 patients. Eight patients were excluded from further analysis (seven elected mastectomy without biopsy; one had an unguided excision). Nineteen of 51 patients with an ipsilateral finding underwent MRI-guided biopsy, which revealed cancer in 11, or 22% of those imaged. Twenty of 53 patients with a contralateral finding underwent MRI-guided biopsy, which revealed cancer in 5, or 9% of those imaged. CONCLUSIONS: MRI of the breast identifies unsuspected multicentric or contralateral cancer in patients with ILC. These findings support the use of MRI in selected patients with ILC, particularly in the ipsilateral breast.

100% inspired oxygen from a Hudson mask-a realistic goal?

BACKGROUND: The administration of oxygen at a high-inspired concentration is often required in medicine, particularly in resuscitation of critically ill patients. However, there is a lack of evidence-based guidance on how to achieve this using currently available apparatus. The aim of this study was to assess how maximum inspired oxygen concentrations can be delivered using existing equipment. METHODS: Ten healthy female volunteers breathed oxygen through two types of Hudson non-rebreathing mask with reservoir bag, one with a safety vent in the mask body and the other with a valve replacing this safety vent (3-valve mask). Oxygen flow was adjusted to either 10 or 15 l min(-1) and the masks were fitted to the face either loosely or tightly. The expired oxygen concentration was measured using an oxygen analyzer. FINDINGS: By using the Hudson non-rebreathing mask with three valves, increasing the oxygen flow to 15 l min(-1), and fitting the mask tightly to the face the average expired oxygen fraction could be raised to 0.85. This equates to an average inspired oxygen fraction of 0.97 in these subjects. INTERPRETATION: The three simple measures mentioned above result in a significant improvement in the performance of the Hudson non-rebreathing mask. Together they allow the delivery of an inspired oxygen concentration close to maximum.

BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1.

Bone morphogenetic proteins play important roles in connective tissue morphogenesis. In this study, we used human multipotential mesenchymal cells as a target to analyze the effect of bone morphogenetic proteins on chondrogenesis. We also analyzed the effect of proinflammatory cytokine interleukin-1 on chondrogenic-differentiated cells and the interaction of IL-1beta with bone morphogenetic proteins. Cells placed in a 3-dimensional matrix of alginate beads and cultured in a serum-free media with bone morphogenetic protein-2 and -9 induced expression of type II collagen (Col2A1) mRNA and increased expression of aggrecan and cartilage oligomeric matrix protein suggesting chondrogenic differentiation of the cells. The transcription factor Sox-9 that regulates both Col2A1 and aggrecan gene expression showed increased expression with BMP treatment. Chondrogenic differentiated cells treated with interleukin-1 decreased Sox-9, Col2A1 and aggrecan gene expression. Removal of interleukin-1 and further addition of bone morphogenetic proteins resulted in returned expression of chondrogenic markers. Chondrogenic differentiated cells cultured in the presence of different concentrations of bone morphogenetic proteins and interleukin-1 showed that bone morphogenetic proteins were able to partially block the suppressive effect of interleukin-1. This study shows that bone morphogenetic proteins play an important role in chondrogenesis and may prove to be potential therapeutics in cartilage repair.

Chondrogenesis in cartilage repair is induced by members of the transforming growth factor-beta superfamily.

The authors recently reported on the principle of an intrinsic repair strategy for partial-thickness articular cartilage defects, which is based on the introduction of a biocompatible and biodegradable matrix loaded with a free chemotactic and mitogenic agent (transforming growth factor-beta 1, at low concentration) and a liposome-encapsulated chondrogenic factor (transforming growth factor-beta 1 at high concentration). In the current study, the potential of other members of the transforming growth factor-beta superfamily (transforming growth factor-beta 2, transforming growth factor-beta 3, bone morphogenetic protein-2 and bone morphogenetic protein-13), and of insulinlike growth factor-1, epidermal growth factor, transforming growth factor-alpha, and Tenascin-C, to induce chondrogenesis within the authors' adult miniature pig articular cartilage defect model, was evaluated. The degree of chondrogenic tissue differentiation was assessed 6 weeks after surgery, on a semiquantitative basis, histologic assessment of cell morphologic features, and intercellular matrix staining being used as the relevant criteria. All selected members of the transforming growth factor-beta superfamily were efficacious in inducing chondrogenic tissue transformation, whereas the other signaling substances tested were not. When encapsulated at high activity levels, bone morphogenetic proteins were less prone than transforming growth factor-beta 1, transforming growth factor-beta 2, and transforming growth factor-beta 3 to evoke undesired side effects as a result of incidental leakage into the joint cavities and subsynovial connective tissue spaces, and therefore they are potentially more suitable candidates for use in human patients.

An apparatus for MR-guided breast lesion localization and core biopsy: design and preliminary results.

System design and initial results are presented from a new unilateral MR-guided breast lesion localization and core biopsy system. Over 150 imaging studies, an accuracy study on phantoms with 50 localization wire deployments and 33 core biopsy trials, and 19 clinical procedures are reported. The mean spatial accuracy from the lesion center for a 20-gauge (G) needle (N = 13) was within 1.2 +/- 1.4 mm (SD) and for a 14G biopsy (N = 4) 0.8 +/- 1.1 mm. For sampling using a 16G core through a 14G needle, the mean accuracy was 5.6 mm (N = 2). The needle guide geometry imposed a small, calculable targeting error. For phantom measurements using the 20G device, the mean geometry-induced error was 0.73 +/- 0.43 mm. However, this contribution was, on average, 42% of the mean measured 2.35 +/- 1.65 mm offset. The new device design provided an accurate and simple guidance method for localization or core biopsy of MR-visible breast lesions.

Cancer staging with breast MR imaging.

Breast MR imaging is a useful tool for staging breast cancer patients, and staging is more accurate with MR imaging than with conventional imaging techniques. MR imaging is the preferred imaging test for the accurate staging of breast cancer before surgery and for assessment of patients with positive axillary adenopathy and negative mammogram and physical examination. There are many important questions regarding the role of MR imaging in breast cancer staging that must be addressed by future research and involvement of MR imaging of the breast in clinical trials.

Observer variability and applicability of BI-RADS terminology for breast MR imaging: invasive carcinomas as focal masses.

OBJECTIVE: The purpose of this study was to assess whether the descriptive terminology and final assessment categories of the Breast Imaging Reporting and Data System (BI-RADS) lexicon can be used for breast carcinomas detected on MR imaging and to assess the inter- and intraobserver variabilities in the use of the descriptors and final assessment categories. MATERIALS AND METHODS: In 82 patients, 101 masses, including 68 infiltrating carcinomas and 33 benign lesions, were interpreted independently by four radiologists and described by BI-RADS terminology with respect to mass shape and margin and BI-RADS final assessment categories. The enhancement pattern of the mass was also reported. In addition, two radiologists interpreted each case twice to evaluate intraobserver variability. The final case set for analysis was the 68 infiltrating carcinomas. RESULTS: Most of the infiltrating carcinomas were described as irregular, spiculated, and heterogeneously enhancing masses. The final impression of the 68 carcinomas was BI-RADS category 5 (highly suggestive of malignancy) in 41 (61%), category 4 (suspicious abnormality) in 24 (35%), and category 3 (probably benign) in three (4%). Enhancement pattern was heterogeneous in 40 (59%), homogeneous in 14 (21%), and rim in 14 (21%). Interobserver agreement was moderate for mass margin, shape, enhancement, and final assessment category. CONCLUSION: This study suggests that the mammographic BI-RADS lexicon with some modifications may be applied to describe the features of infiltrating carcinoma seen on breast MR imaging.

Bracketing wires for preoperative breast needle localization.

OBJECTIVE: The purpose of this study was to evaluate the outcomes of bracketing wire placement during preoperative breast needle localization. SUBJECTS AND METHODS: We prospectively examined mammograms of 1057 consecutive lesions that had preoperative needle localization and surgical excision and classified the lesions according to Breast Imaging Reporting and Data System (BI-RADS) final assessment categories. Bracketing wires, defined as multiple wires placed to delineate the boundaries of a single lesion, were used in 103 (9.7%) of 1057 lesions. Medical records, imaging studies, and histologic findings in these 103 lesions were reviewed. RESULTS: Of 103 bracketed lesions, median lesion size was 3.5 cm (range, 1.5-9.5 cm). Ninety-three lesions (90.3%) contained calcifications; 65 lesions (63.1%) were BI-RADS category 5 (highly suggestive of malignancy); and 33 lesions (32.0%) were percutaneously proven cancers. The median number of wires placed was two (range, 2-5). Surgical histologic findings were carcinoma in 75 lesions (72.8%), atypical hyperplasia in eight lesions (7.8%), and benign in 20 lesions (19.4%). Of 42 calcific lesions that were bracketed and had postoperative mammograms available for review, complete removal of suspicious calcifications was accomplished in 34 (81.0%). Of 75 cancers that were bracketed, clear histologic margins of resection were obtained in 33 (44.0%). CONCLUSION: Bracketing wires were used during preoperative needle localization primarily for larger calcific lesions that were proven cancers or were highly suggestive of malignancy (BI-RADS category 5). Bracketing wires may assist the surgeon in achieving complete excision of calcifications, but bracketing wires do not ensure clear histologic margins of resection.