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Chemotherapy in non-small cell lung cancer: a review.

Lung cancer, of which non-small cell carcinoma is the most common, has been a significant therapeutic challenge for decades and will remain so for decades to come. Despite its prevalence, progress in the management of non-small cell lung cancer has been relatively slow. This is in part due to the pessimism of most physicians treating this disease, which has resulted in a relatively lackadaisical attitude with regards to clinical trials when compared to other solid tumours like breast or colorectal cancers. Nevertheless, the past decade has seen significant progress, specifically with regards to the management of locally advanced disease. Chemotherapy, though shown to be biologically active in non-small cell lung cancer, is considered an ineffective palliative tool in the setting of metastatic disease due to its toxicities and the "less than encouraging" response rates generated by the cisplatin-based combination regimen which is generally considered to be the most active currently available. The advent of new active agents such as paclitaxel and vinorelbine which are potentially less toxic may change this view. Conversely, the response rate of locally advanced disease to chemotherapy is significantly higher and this has resulted in numerous multimodality trials of neoadjuvant chemotherapy prior to surgery and/or radiation. To date, a number of randomised trials have shown that this approach can result in significant survival benefit for patients with locally advanced disease. An alternative approach makes use of the potential synergism between certain chemotherapeutic agents (such as cisplatin) and radiation when used concurrently. However, data on concurrent chemoradiotherapy in locally advanced disease have been largely based on single-arm studies and are inconclusive. Three randomised trials on concurrent chemoradiotherapy have been shown benefit for the use of combined modality in locally advanced disease. Hence, treatment of locally advanced disease should include chemotherapy as part of the combined modality approach. However, the optimal sequencing of these modalities would require well-designed randomised trials to determine.

Antineoplastic Combined Chemotherapy Protocols↗

Impact of Bt corn on rhizospheric and soil eubacterial communities and on beneficial mycorrhizal symbiosis in experimental microcosms.

A polyphasic approach has been developed to gain knowledge of suitable key indicators for the evaluation of environmental impact of genetically modified Bt 11 and Bt 176 corn lines on soil ecosystems. We assessed the effects of Bt corn (which constitutively expresses the insecticidal toxin from Bacillus thuringiensis, encoded by the truncated Cry1Ab gene) and non-Bt corn plants and their residues on rhizospheric and bulk soil eubacterial communities by means of denaturing gradient gel electrophoresis analyses of 16S rRNA genes, on the nontarget mycorrhizal symbiont Glomus mosseae, and on soil respiration. Microcosm experiments showed differences in rhizospheric eubacterial communities associated with the three corn lines and a significantly lower level of mycorrhizal colonization in Bt 176 corn roots. In greenhouse experiments, differences between Bt and non-Bt corn plants were detected in rhizospheric eubacterial communities (both total and active), in culturable rhizospheric heterotrophic bacteria, and in mycorrhizal colonization. Plant residues of transgenic plants, plowed under at harvest and kept mixed with soil for up to 4 months, affected soil respiration, bacterial communities, and mycorrhizal establishment by indigenous endophytes. The multimodal approach utilized in our work may be applied in long-term field studies aimed at monitoring the real hazard of genetically modified crops and their residues on nontarget soil microbial communities.

Bacillus thuringiensis↗

Diuretic contrast-enhanced magnetic resonance urography versus intravenous urography for depiction of nondilated urinary tracts.

Diuretic contrast-enhanced magnetic resonance urography (MRU) is analogous to conventional intravenous urography (IVU) and, hence, designated as excretory MRU. It is performed with a T1-weighted fast gradient-echo sequence to obtain breath-hold, dynamic MRU after intravenous injection of low-dose furosemide (5-10 mg) and gadolinium (Gd) chelate. The combination of Gd and furosemide is the key for achieving a uniform distribution of the contrast material inside the entire urinary tract. It provides high-resolution images of nondilated urinary tracts and information about the renal function. This pictorial essay reviews the technical aspects and practical consideration of diuretic Gd-enhanced MRU and underlines its diagnostic capability in comparison with IVU in the depiction of nondilated collecting systems. We discuss its potential applications, as in young patients with anatomic anomalies, patients with renal transplants, patients allergic to iodinated contrast medium, and avoiding multimodality work-up in the evaluation of kidney donors and patients with renal and extrarenal tumor diseases.

Adult↗

A multi-modal survival prediction framework with group-based batch training and structural consistency alignment.

OBJECTIVE: Integrating whole-slide images (WSIs) with transcriptomic profiles is pivotal for enhancing cancer survival prediction. However, the intrinsic gigapixel resolution and variable sequence lengths of WSIs create a fundamental trade-off between training efficiency and the preservation of data heterogeneity in existing frameworks. Furthermore, substantial statistical and structural discrepancies between histological and genomic modalities often impede effective cross-modal alignment and fusion, thereby limiting prognostic accuracy. METHODS: We propose PRISM, an efficient multi-modal learning framework for integrating WSIs with transcriptomic profiles. To reconcile training efficiency with full data heterogeneity, PRISM first stochastically partitions variable-length WSI sequences into a main subset and a complementary residual subset, both of which are packed into fixed-length groups for batch training. The main subset is processed in the main branch, utilizing isolation masking to maintain intra-group sequence independence. Simultaneously, the residual subset is consolidated into "hyperslides" within a residual branch that leverages tailored supervision, effectively capturing inter-slide correlations. Furthermore, PRISM integrates an Informative Token Aggregation (ITA) module to reduce redundancy in WSIs and employs Cross-batch Structural Consistency Alignment (CBSCA) mechanism to enhance inter-modal structural connectivity. Finally, efficient cross-modal feature interaction is achieved through a Low-rank Bilinear Gated Fusion (LBGF) module. Code is available at https://github.com/Alisa2080/PRISM. RESULTS: Compared with existing methods, PRISM achieves the best overall C-index across five TCGA cohorts. On the larger TCGA-BRCA dataset, PRISM requires only 6 hours of training time, substantially reducing computational cost relative to strong multimodal baselines. Furthermore, comprehensive evaluations demonstrate that PRISM achieves the best overall IBS ranking and favorable time-dependent AUC performance at 1, 3, and 5 years, thereby delivering a more favorable trade-off between prognostic performance and computational efficiency. CONCLUSION: PRISM provides a favorable balance between predictive performance, calibration quality, and computational efficiency, highlighting its potential for practical deployment in multimodal survival modeling for computational pathology.

Humans↗

Modulation of the atypical multidrug-resistant phenotype by a hammerhead ribozyme directed against the ABC transporter BCRP/MXR/ABCG2.

The phenomenon of multidrug resistance (MDR) in human cancers is one of the major causes of failure of chemotherapy. A recently identified new member of the superfamily of ATP-binding cassette transporters, breast cancer resistance protein (BCRP), was demonstrated to confer an atypical multidrug-resistant phenotype to tumor cells. To overcome the BCRP-mediated drug resistance, a specific anti-BCRP hammerhead ribozyme was introduced into the human gastric carcinoma cell line, EPG85-257RNOV, exhibiting an atypical MDR phenotype. By this approach, the expression levels of the targeted BCRP-encoding mRNA and the BCRP transport protein were decreased to the low constitutive expression level that was observed in highly drug-sensitive parental gastric carcinoma cells. In addition, in the anti-BCRP ribozyme-treated cells, the cellular drug accumulation was dramatically increased to the level measured in drug-sensitive cells. These effects were accompanied by an extensive reversal of the drug-resistant phenotype of more than 80%. Because additional mechanisms contribute to the multimodal-mediated MDR phenotype exhibited by this gastric carcinoma cell line, the data suggest that the BCRP-mediated contingent to the drug resistance was overcome nearly completely. Moreover, the data indicate that ribozyme-based gene therapy may be clinically applicable in preventing and reversing BCRP-mediated atypical MDR.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

Treatment of malignant mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare tumor that predominantly afflicts men over 50 years of age. Nearly 3000 MPMs are reported annually in the United States with the incidence expected to rise into the new millenium. Over the past 40 years, MPM has been unequivocally linked to asbestos exposure worldwide. Recently, however, a new theory on the carcinogenesis of this tumor has been proposed with the isolation of a simian virus (SV 40)-like gene sequence in mesothelioma tumor cells. The clinical presentation of MPM is variable, although most patients typically present with dyspnea, chest pain, or pleural effusion. Obtaining a diagnosis of MPM has been greatly assisted by video-assisted surgery and the use of immunohistochemistry and electron microscopic techniques, which help distinguish MPM from other tumor pathologies such as adenocarcinoma. Computed tomography and magnetic resonance imaging have been also useful for determining tumor burden and resectability. Traditionally, strategies for the treatment of MPM have included supportive care, surgery, radiotherapy, and chemotherapy. Survival with supportive care alone ranges between 4 and 12 months. Single-modality therapy using traditional approaches (surgery, radiotherapy, chemotherapy) alone has failed to improve patient survival significantly. Recently, results using a multimodality approach have been favorable. In particular, cytoreductive surgery (pleuropneumonectomy) followed by sequential chemotherapy and radiotherapy have demonstrated improved survival, especially for patients with epithelial histology, negative resection margins, and no metastases to extrapleural lymph nodes. Innovative therapies such as the use of photodynamic, targeted cytokines and gene therapy are currently being investigated for management of MPM.

Combined Modality Therapy↗

Mechanism of O-antigen distribution in lipopolysaccharide.

O-antigen units are nonuniformly distributed among lipid A-core molecules in lipopolysaccharide (LPS) from gram-negative bacteria, as revealed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate; the actual distribution patterns are complex, multimodal, and strain specific. Although the basic biochemical steps involved in synthesis and polymerization of O-antigen monomers and their subsequent attachment to lipid A-core are known, the mechanism by which specific multimodal distribution patterns are attained in mature LPS has not been previously considered theoretically or experimentally. We have developed probability equations which completely describe O-antigen distribution among lipid A-core molecules in terms of the probability of finding a nascent polymer (O antigen linked to carrier lipid) of length k (Tk) and the probability that a nascent polymer of length k will be extended to k + 1 by polymerase (pk) or transferred to lipid A-core by ligase (qk). These equations were used to show that multimodal distribution patterns in mature LPS cannot be produced if all pk are equal to p and all qk are equal to q, conditions which indicate a lack of selectivity of polymerase and ligase, respectively, for nascent O-antigen chain lengths. A completely stochastic model (pk = p, qk = q) of O-antigen polymerization and transfer to lipid A-core was also inconsistent with observed effects of mutations which resulted in partial inhibition of O-antigen monomer synthesis, lipid A-core synthesis, or ligase activity. The simplest explanation compatible with experimental observations is that polymerase or ligase, or perhaps both, have specificity for certain O-antigen chain lengths during biosynthesis of LPS. Our mathematical model indicates selectively probably was associated with the polymerase reaction. Although one may argue for a multimodal distribution pattern based on a kinetic mechanism i.e., varying reaction parameters in space or in time during cell growth, such a model requires complex sensory and regulatory mechanisms to explain the mutant data and mechanisms for sequestering specific components of LPS biosynthesis to explain the distribution pattern in normal cells. We favor the simple alternative of enzyme specificity and present generalized equations which should be useful in analysis of other analogous biochemical systems.

Antigens, Bacterial↗

Identification of EGFR mutations in esophageal cancer.

BACKGROUND: It is well known that the prognosis for esophageal cancer is worse than for other digestive cancers in spite of multimodality treatment, and there is an urgent need to improve this situation. The epidermal growth factor receptor (EGFR) inhibitor, gefitinib, was approved in Japan to treat advanced non-small cell lung cancer patients and several papers have since reported that the successfully treated patients had genetic mutations in EGFR. PURPOSE: The aim of this study was to investigate the existence of EGFR mutations in esophageal cancer cell lines and primary lesions, and also to explore the possibility of treating esophageal cancer using gefitinib. MATERIALS AND METHODS: Nineteen esophageal cancer cell lines were cultured and DNA was extracted using an ultracentrifugation method. Fifty cases of primary cancer and corresponding normal tissue samples were obtained and DNA was extracted using the same protocol. Nested PCR and DNA sequencing targeting exons 18, 19, 20 and 21 of EGFR were performed to investigate the presence of mutations in esophageal cancer cell lines and primary tumors. RESULTS: Three of the 19 cell lines had the same silent mutation at nucleotide 2607, a G-to-A substitution in exon 20. One of the 50 patients had an EGFR mutation in codon 719, resulting in an amino acid substitution from glycine to aspartic acid. CONCLUSION: EGFR mutations in esophageal carcinoma are rare but do exist, and thus gefitinib could be included in esophageal cancer treatment regimens by selecting those patients who possess such mutations.

Biomarkers, Tumor↗

Imaging of proteolytic activity using a conditional cell surface receptor.

Programmed cell death (apoptosis) is a ubiquitous means utilized by multicellular organisms for elimination of unwanted cells during development and homeostasis. Dysregulated apoptosis is implicated in an array of clinical disorders including cancer, autoimmune diseases, neurodegenerative disorders, and ischemia. During programmed cell death, a series of proteases, known as caspases, with different specificities play crucial roles in the apoptotic process. Caspase-3, a group II cysteine aspartate protease, recognizes and cleaves substrates harboring the amino acid sequence aspartic acid-glutamic acid-valine-aspartic acid (DEVD), and it plays an important role in the terminal phase of apoptosis. Here we report the development of a novel imaging platform for sensing the activation of cellular proteases. A recombinant chimeric protein was constructed, composed of a cell-surface-targeted single-chain antibody (sFv) fused to a Golgi retention signal. The DEVD tetrapeptide sequence was included between the single-chain antibody and the Golgi retention signal as a caspase-3 protease cleavage site. When expressed in cultured cells this fusion protein was localized to Golgi bodies and was not detected on the cell surface. Induction of apoptosis resulted in cleavage of the fusion protein releasing the single-chain antibody from the Golgi retention signal in a caspase-dependent manner. As a result, in cells undergoing apoptosis the single-chain antibody was visualized at the cell surface by immunofluorescence microscopy. The expression of sFv on the surface of cells in a protease-dependent manner provides a unique opportunity for real-time imaging through the use of targeted nanoparticles. This methodology may provide for a multimodal noninvasive real-time imaging of apoptosis and a new opportunity for high-throughput screening of cell-death-modulating therapeutic agents.

Animals↗

Affiliative processes and vocal development.

Affiliative behavior is often expressed through communication, and the nature of affiliative interactions affects the ontogeny of communication. I presented three phenomena that demonstrate the importance of affiliation in vocal development in marmosets and tamarins, but the results have parallels in many other species including birds, dolphins, and humans. Pygmy marmosets use trill-like vocalizations to maintain contact with other group members. Individuals change subtle aspects of call structure when they encounter new social groups or acquire a new mate. This process of vocal accommodation is common in many other species. Infant pygmy marmosets go through a stage of "babbling." producing long sequences of vocalizations that have several similarities to the babbling of human infants. Babbling infants receive more social attention than nonbabbling infants, and these social interactions may shape vocalizations towards more adult forms. In adult cotton-top tamarins, food-associated vocalizations communicate the presence and quality of food. However, reproductively inhibited juveniles and subadults use many other types of calls in feeding situations and display a high proportion of imperfect forms of adult food-associated calls. When subadult monkeys are paired with new mates and change their reproductive status, they rapidly (within 3-6 weeks) display both adult structure and adult usage of food-associated calls, suggesting that affiliative processes can both facilitate and inhibit vocal ontogeny. Three mechanisms of how social interactions affect communication (multimodal stimulation, attentional focus, and reinforcement) were proposed and illustrated through examples of parrots learning English labels for objects and attributes and infant cotton-top tamarins acquiring food-associated vocalizations.

Animals↗

Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer.

Combined chemotherapy and thoracic radiation therapy has emerged as a primary treatment option for locally advanced, unresectable non-small cell lung cancer (NSCLC). Randomized trials and subsequent metaanalyses have shown a clear survival benefit with platinum-based combination chemotherapy administered sequentially or concurrently with hyperfractionated thoracic radiation over radiation alone. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin recently have been evaluated in numerous phase 1/11 trials at various doses in both sequential and concurrent schedules with thoracic radiation in patients with locally advanced and unresectable NSCLC. The patterns of failure in patients treated with concurrent paclitaxel/carboplatin and thoracic radiation suggest the need for additional chemotherapy either at the front end or after completion of the concurrent regimen. A large multicenter randomized study (Locally Advanced Multimodality Protocol) has been initiated to address these issues of improvement in distant control and to further refine the combined-modality approach for patients with locally advanced NSCLC. Several other combined-modality regimens incorporating a platinum compound and a novel agent like gemcitabine, vinorelbine, paclitaxel, or docetaxel have been recently completed or are in progress. The hope for the immediate future is to define an "effective" and "optimal" regimen that can be given simultaneously with thoracic radiation and can result in improved local and systemic control in patients with regionally advanced NSCLC. Numerous phase II and III trials are currently planned or under way to further define the efficacy of this novel combination of paclitaxel/carboplatin in combined-modality programs in an attempt to determine the optimal administration sequence of chemotherapy and thoracic radiation. These combined-modality programs are now being integrated into trials for early stage, potentially resectable disease. Thus, NSCLC is in fact a systemic disease requiring a multidisciplinary approach for optimal management.

Antineoplastic Combined Chemotherapy Protocols↗

Comparison of theoretical proteomes: identification of COGs with conserved and variable pI within the multimodal pI distribution.

BACKGROUND: Theoretical proteome analysis, generated by plotting theoretical isoelectric points (pI) against molecular masses of all proteins encoded by the genome show a multimodal distribution for pI. This multimodal distribution is an effect of allowed combinations of the charged amino acids, and not due to evolutionary causes. The variation in this distribution can be correlated to the organisms ecological niche. Contributions to this variation maybe mapped to individual proteins by studying the variation in pI of orthologs across microorganism genomes. RESULTS: The distribution of ortholog pI values showed trimodal distributions for all prokaryotic genomes analyzed, similar to whole proteome plots. Pairwise analysis of pI variation show that a few COGs are conserved within, but most vary between, the acidic and basic regions of the distribution, while molecular mass is more highly conserved. At the level of functional grouping of orthologs, five groups vary significantly from the population of orthologs, which is attributed to either conservation at the level of sequences or a bias for either positively or negatively charged residues contributing to the function. Individual COGs conserved in both the acidic and basic regions of the trimodal distribution are identified, and orthologs that best represent the variation in levels of the acidic and basic regions are listed. CONCLUSION: The analysis of pI distribution by using orthologs provides a basis for resolution of theoretical proteome comparison at the level of individual proteins. Orthologs identified that significantly vary between the major acidic and basic regions maybe used as representative of the variation of the entire proteome.

Bacterial Proteins↗

In vivo targeting of underglycosylated MUC-1 tumor antigen using a multimodal imaging probe.

One of the most difficult challenges of oncology is to improve methods for early tumor detection, which is crucial for the success of cancer therapy and greatly improves the survival rate. Underglycosylated mucin-1 antigen (uMUC-1) is one of the early hallmarks of tumorigenesis and is overexpressed and underglycosylated on almost all human epithelial cell adenocarcinomas as well as in nonepithelial cancer cell lines, as well as in hematological malignancies such as multiple myeloma, and some B-cell non-Hodgkin lymphomas. In this study, we designed, synthesized, and tested a novel multimodal imaging probe specifically recognizing in vivo uMUC-1 antigen in an animal model of human cancer. Furthermore, in vivo magnetic resonance- and near-infrared-imaging experiments on tumor-bearing animals showed specific accumulation of the probe in uMUC-1-positive tumors and virtually no signal in control tumors. We expect that this probe has a potential to greatly aid in screening prospective patients for early cancer detection and in monitoring the efficacy of drug therapy.

Amino Acid Sequence↗

[Multimodal therapy of rectal carcinoma].

Multimodal therapy for rectal carcinoma is--in contrast to colon cancer--largely based on adjuvant or neoadjuvant radiotherapy. Although radiotherapy reduces local recurrence rates, overall survival is hardly improved, while on the other hand specific complications of radiotherapy are recognized. Extended neoadjuvant treatment concepts including chemotherapy may improve long-term outcome, but to date this has not been demonstrated conclusively by randomized trials. New developments include intraoperative radiotherapy and the combination of hyperthermia with radiochemotherapy. Initial results from randomized studies are promising, but require confirmation by larger trials. At the same time the importance of optimal surgical treatment has been recognized as a prerequisite for favourable long-term results. Since this aspect has not received due attention in past protocols the optimal combination of surgery with other modalities and their time sequence cannot be determined presently.

Chemotherapy, Adjuvant↗

Spatiotemporal mapping of tertiary lymphoid structure heterogeneity shapes immune niches and clinical outcomes in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy with limited therapeutic options. The spatial architecture and functional diversity of tertiary lymphoid structures (TLSs) in iCCA remain unclear. Here, we present a multimodal spatial atlas of TLSs and identified intratumoral TLSs (iTLSs) as independent prognostic markers. Bulk proteomic profiling of 214 discovery and 155 validation cases identified a four-tier TLS-based tumor microenvironment classification system and supported development of a TLS-predictive random forest classifier. Imaging mass cytometry revealed that iTLS+ tumors harbor structured immune architectures, where M1-like tissue-resident macrophages (RTMs), dendritic cells, and CXCL13+ CD4+ T cells colocalize to form antigen-presenting neighborhoods (apc-CNs) spatially coupled to TLS core regions (TLScore-CNs). Single-cell spatial transcriptomics further resolved 61 TLSs into 14 spatial niches and defined a pseudotemporal maturation continuum: aggregated, activated, and postactivated. Intraniche communication, primarily mediated by ifnCAFs, iCAFs, and CXCL12+ macrophages, evolved dynamically with maturation. Single-nucleus RNA sequencing combined with Tangram-based spatial mapping revealed CXCL12+ macrophages and iCAFs forming a peripheral band in aggregated TLSs, whereas ifnCAFs infiltrated TLS interiors during activation. These findings define TLS heterogeneity and provide insights for stroma-directed immunotherapy.

Cholangiocarcinoma↗

In vivo phage display selection yields atherosclerotic plaque targeted peptides for imaging.

PURPOSE: Atherosclerosis is a leading cause of morbidity and mortality in the Western world, yet specific imaging agents to detect and map inflammatory plaques are still lacking. PROCEDURES: We used in vivo phage display to interrogate early atherosclerotic lesions present in ApoE-/- mice with the goal of identifying plaque-associated endothelial cell internalized affinity ligands. RESULTS: We identified 30 phage families with some of these families exhibiting homology to known atherosclerotic proteins, namely, leukemia inhibitory factor, transferrin, and VLA-4. VLA-4 homologous peptides [termed vascular cellular adhesion molecule-1 (VCAM-1) internalizing peptide-28 (VINP28)] bound to and were internalized by VCAM-1-expressing cells and were inhibited by soluble VCAM-1. In addition, a VINP28 modified multimodal nanoparticle showed high affinity for endothelial cells expressing VCAM-1 but low affinity for macrophages or smooth muscle cells. CONCLUSION: The identified peptides represent a set of probes to interrogate the cell surface repertoire and potentially allow early detection of atherosclerosis.

Affinity Labels↗

Integration of hydrodynamic and odorant inputs by local interneurons of the crayfish deutocerebrum.

Intracellular electrodes were used to record from local interneurons in the olfactory lobes of the midbrain in the crayfish Procambarus clarkii. Cells that resembled previously studied central targets of olfactory receptor neurons on the lateral antennular flagellum were specifically examined for their responses to hydrodynamic stimuli. Initiation of water movement past the antennular flagellum, confined within an olfactometer, evoked a triphasic excitatory-inhibitory-excitatory postsynaptic potential lasting up to 2 s that generated spikes on depolarizing phases of the response sequence. Odorant pulses seamlessly imbedded in the water pulse past the antennule evoked purely excitatory, dose-dependent postsynaptic responses and associated spike trains. The latency of the initial phase of the response to water was approximately half as long as the latency of the response to odorant, suggesting that different afferent pathways are involved in responses to hydrodynamic and odorant stimuli, respectively. In some olfactory lobe interneurons that resembled previously described cells classified as Type I, conjoint stimulation of fluid onset and odorant evoked responses that were twice the amplitude of the summed response to either hydrodynamic or odorant stimulation alone, suggesting that the olfactory responses were potentiated by hydrodynamic input. Individuals of at least one other class of first-order interneuron that responded to both hydrodynamic and odorant stimulation were occasionally recorded from. These results indicate that multimodal integration of chemical and mechanical information occurs at the level of first-order sensory interneurons in the crayfish brain.

Animals↗

Imaging in ureteral complications of renal transplantation: value of static fluid MR urography.

Ureteral obstruction is an infrequent complication after renal transplantation that may cause rapid loss of transplant function. We tested static fluid MR urography for determining the cause of graft hydronephrosis. Magnetic resonance urography was performed in nine transplants with dilated collecting systems on ultrasound. A heavily T2-weighted 3D turbo spin-echo sequence on a 1.5-T scanner was used and maximum intensity projections were obtained. The patients also underwent excretory urography (n = 1), renal scintigraphy (n = 1), antegrade pyelography (n = 3), voiding cystourethrography (n = 4), and non-enhanced CT (n = 2). Six patients had pathologic conditions including ureteral stricture, compression by lymphoceles, implantation stenosis, vesicoureteral reflux, and late-occurring transitional cell carcinoma at the implantation site. Static MRU was able to diagnose or exclude a dilation of the graft collecting system. It visualized the course of the ureters and localized the obstruction site in four of five obstructed transplants. In one case the ureter was obscured by lymphoceles, which were demonstrated by hydrographic MRU as well. The definite cause for obstruction was provided in only 2 of 5 cases. Dilation due to vesicoureteral reflux could not be differentiated. The current multimodality approach to renal transplant imaging already provides comprehensive assessment of graft hydronephrosis. Static MRU may be useful in some cases since complications associated with intravenous iodinated contrast or antegrade pyelography can be avoided. Its main drawback, the lack of functional information, may be overcome by combining it with contrast-enhanced MRU.

Adult↗