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The integration of new therapies and radiation in the management of ovarian cancer.

New biologic information has led to a therapeutic program in Stage III ovarian cancer that considers the whole peritoneal cavity the tumor-bearing region and that uses intraperitoneal administration of ovarian cancer antiserum, intraperitoneal P-32, delayed split abdominal irradiation, and chemotherapy. The survival for those patients completing irradiation was 85%. Forty-nine patients with advanced (Stage III, IV, or recurrent) ovarian cancer have been treated with combinations of the present agents. Twenty-two patients have received intraperitoneal ovarian cancer antiserum without significant toxicity. Extensive staging has been a requirement for initial evaluation and includes maximal surgical resection, omentectomy, TAH and BSO, nodal biopsies, and peritoneal cytology. Nineteen patients had 5-mm nodules or less residual disease and were treated with colloidal P-32, abdominal irradiation, and chemotherapy; five of these patients received intraperitoneal antiserum before cytotoxic therapy. The four-year cumulative survival is 84%, and the disease-free survival 43%. A randomized prospective study is now examining the value of antiserum therapy. New experimental data from our laboratory indicate 1) the value of 2/3 biomarkers (alpha globulin and free secretory protein) in following patients for remission of disease and 2) the probability of the development of more effective antiserum with high specific titer. Studies of the radiosensitivity of ovarian cancer indicate the tumor was not different from other solid tumors. Our studies indicate the role of radiation therapy as a cytoreductive agent should be integrated in multimodality therapy and that the immune system offers new possibilities in amplifying therapeutic results.

Alpha-Globulins↗

Giant neurons in the caudal pontine reticular formation receive short latency acoustic input: an intracellular recording and HRP-study in the rat.

The reticular formation is composed of heterogeneous cell populations with multiple functions. Among these multiple functions is the processing of sensory information in the context of behavior. The purpose of the present study was to identify and characterize neurons in the reticular formation of the rat that receive auditory input. In order to do so, we combined intracellular electrophysiology in vivo with intracellular injection of horseradish peroxidase, enabling us to correlate electrophysiology unequivocally with anatomy at the single cell level. We found that many neurons in the caudal pontine reticular nucleus (PnC), which we analyzed intracellularly, responded to acoustic stimuli and were excited at short latency (mean EPSP latency: 2.6 ms; mean spike latency: 5.2 ms). This short latency suggests a direct input from the cochlear nucleus, the first central nucleus of the auditory pathway. The morphology revealed that the acoustically driven PnC neurons have very large somata (mean diameter: 44.0 microns). They can therefore be referred to as "giant PnC neurons." Complex dendritic arbors extended from these neurons into the reticular formation and thus formed a large membrane surface for the integration of multimodal inputs. Most of the giant PnC neurons sent their axons caudally into the medial longitudinal fasciculus and can therefore be regarded as reticulospinal neurons. The results demonstrate that the giant reticulospinal PnC neurons are in a position to transmit acoustic information very quickly to spinal cord neurons and to receive converging input from other parts of the brain. They are thus good candidates for participation in the mediation and modulation of acoustically elicited behaviors, such as the short latency acoustic startle response.

Acoustic Stimulation↗

Radiological diagnosis of skeletal metastases.

The clinical management of patients with skeletal metastases puts new demands on imaging. The radiological imaging in screening for skeletal metastases entails detection, metastatic site description and radiologically guided biopsy for morphological typing and diagnosis. Regarding sensitivity and the ease in performing surveys of the whole skeleton, radionuclide bone scintigraphy still is the first choice in routine follow-up of asymptomatic patients with metastatic disease of the skeleton. A negative scan has to be re-evaluated with other findings, with emphasis on the possibility of a false-negative result. Screening for metastases in patients with local symptoms or pain is best accomplished by a combination of radiography and MRI. Water-weighted sequences are superior in sensitivity and in detection of metastases. Standard spin-echo sequences on the other hand are superior in metastatic site description and in detection of intraspinal metastases. MRI is helpful in differentiating between malignant disease, infection, benign vertebral collapse, insufficiency fracture after radiation therapy, degenerative vertebral disease and benign skeletal lesions. About 30% of patients with known cancer have benign causes of radiographic abnormalities. Most of these are related to degenerative diseases and are often easily diagnosed. However, due to overlap in MRI characteristics, bone biopsy sometimes is essential for differentiating between malignant and nonmalignant lesions. Performing bone biopsy and aspiration cytology by radiologist and cytologist in co-operation has proven highly accurate in diagnosing bone lesions. The procedure involves low risk to the patient and provides a morphological diagnosis. Once a suspected metastatic lesion is detected, irrespective of modality, the morphological diagnosis determines the appropriate work-up imaging with respect to the therapy alternatives. The integration of multimodality imaging in the assessment of skeletal metastases is complex and requires multidiciplinary co-operation in order to optimize screening and medical clinical care with respect to the prognosis and life quality of patients with bone metastatic disease.

Biopsy↗

Distribution and functional significance of Met-enkephalin-Arg6-Phe7- and Met-enkephalin-Arg6-Gly7-Leu8-like peptides in the blowfly Calliphora vomitoria. I. Immunocytochemical mapping of neuronal pathways in the brain.

Neuronal pathways immunoreactive to antisera against the extended-enkephalins, Met-enkephalin-Arg6-Phe7 (Met-7) and Met-enkephalin-Arg6-Gly7-Leu8 (Met-8), have been identified in the brain of the blowfly Calliphora vomitoria. Co-localisation with other enkephalins in certain neurons suggests that a precursor similar to preproenkephalin A exists in insects and that differential enzymatic processing occurs as in vertebrates. Co-localisations of the extended-enkephalin-like peptides with other vertebrate-type peptides, including cholecystokinin and pancreatic polypeptide, also occur. The enkephalinergic pathways are specific, comprising a few groups of highly characteristic neurons and areas of neuropil. Of special interest is the finding that parts of the antennal chemosensory and the optic lobe visual systems contain Met-8 immunoreactive neurons. Within the median neurosecretory cell groups, some of the giant neurons show immunoreactivity to Met-8 and others to both Met-8 and Met-7. Fibres from these cells project to the corpus cardiacum and also to the suboesophageal ganglion, where arborisations occur in the tritocerebral neuropil. Co-localisation studies of these cells have shown that at certain terminals, one particular type of peptide is the dominant neuroregulator, whilst at other terminals, within the same cell, a different co-synthesised peptide predominates. Several groups of lateral neurosecretory cells show clearly defined enkephalinergic pathways, most of which have connections with the central body. The complex patterns of immunoreactivity seen in terminals in the different parts of the central body, suggest an important role for the enkephalin-like peptides in the integration of multimodal sensory inputs. The physiological functions of the extended-enkephalin-like peptides in the brain of Calliphora is still unknown, but the anatomical evidence suggests they may have a role similar to that in mammals, where they are thought to control aspects of feeding behaviour.

Animals↗

[Recall dermatitis caused by re-exposure to docetaxel following irradiation of the brain. Case report and review of the literature].

BACKGROUND: Together with radiation therapy the taxanes Paclitaxel and Docetaxel are more and more integrated into multimodal therapy regimens concerning breast- and lung cancer as well as squamous cell carcinoma of the head and neck. Especially in palliative situations we have to be aware of increasing side effects caused by interaction of the different treatment components. Therefore we report on a severe recall dermatitis that occurred in two breast-cancer patients following irradiation of the brain and reexposition to Docetaxel. PATIENTS AND METHOD: From January until March 1999 two female patients suffering from metastatic breast cancer and newly diagnosed cerebral metastases respectively carcinomatous meningitis underwent irradiation of the whole brain (2 Gy 5 days/week up to a reference dose of 50 Gy) in our department. Both patients had several courses of Docetaxel (Taxotere) 30 mg/m2 BSA weekly respectively 100 mg/m2 BSA/month since October and November 1998. After completion of radiotherapy chemotherapy with Docetaxel was continued. RESULTS: Both patients tolerated Docetaxel well before and during radiotherapy. However, after having finished irradiation of the brain and receiving Docetaxel again a severe erythema of the irradiated skin and large areas of moist epitheliolysis with crust occurred (CTC grade IV). CONCLUSION: The dermatitis related to irradiation and reexposition to Docetaxel observed in our two cases is interpreted as a recall reaction. The basic initiating pathologic mechanism has not been solved completely. Further investigation is needed to find out how the taxanes can be used in combination radiochemotherapy regimens without causing severe toxicity to the irradiated skin or mucosa.

Aged↗

Osteoarthritis phenotypes: advancing precision medicine through clinical, structural, and molecular stratification.

PURPOSE: Osteoarthritis (OA) is now understood as a heterogeneous syndrome driven by diverse biological, biomechanical, metabolic, genetic, and molecular mechanisms. This variability explains differences in disease progression and treatment response, challenging the traditional "one-size-fits-all" approach. This review highlights OA phenotyping as a key step toward precision medicine, focusing on clinical, structural, and molecular classifications that inform individualized care. METHODS: A narrative review was conducted using a non-systematic search of major databases and Osteoarthritis Research Society International sources (2010-2026). Evidence was thematically synthesized across clinical, imaging, and molecular domains to characterize OA phenotypes and their potential relevance to precision medicine. RESULTS: Multiple OA phenotypes were identified: inflammatory, metabolic, biomechanical, cartilage-subchondral, pain-sensitization, and aging/senescence. These exhibit distinct clinical features, risk factors, and therapeutic responses. Imaging-based phenotypes (e.g., inflammatory, meniscus-cartilage, subchondral bone, atrophic, hypertrophic) and molecular endotypes (low turnover, structural damage, systemic inflammation) further refine stratification. Pain-structure discordance is notable in sensitization phenotypes and may predict poorer surgical outcomes. Joint-specific variations and emerging genomic and epigenetic insights underscore disease complexity. Advances in imaging, biomarkers, and machine learning may enable earlier detection and patient clustering, though clinical application remains limited. CONCLUSION: Phenotype- and endotype-based classification represents a critical advancement toward precision OA management. Tailored interventions based on stratification hold promise for improving outcomes; however, clinical translation remains limited by overlapping phenotypes, lack of validated biomarkers, and inconsistent results from phenotype-driven trials. Wider clinical adoption requires standardized definitions, validation across joints, and integration of multimodal diagnostic tools into routine practice.

Humans↗

[Limited efficacy of opioids in chronic musculoskeletal pain].

After excluding malignant disease in 21 patients with unremitting strong pain of the musculoskeletal system despite long-term opioid medication, the opioids were withdrawn to search for reasons of the limited effectiveness of the opioids. The opioid withdrawal was integrated in multimodal pain coping therapy. Besides the somatic diagnoses, pain-relevant psychosomatic diagnoses were evaluated with the structured clinical interview for DSM-IV (SCID). At the time of admission and discharge pain medication, physical functions, mood, and pain intensity were recorded. In the SCID interview, all patients were diagnosed with a relevant comorbid psychiatric condition (pain disorder, anxiety, depression). Despite reduction of the opioid medication, there was no increase of pain, but an improvement of the physical functions. In patients with chronic pain of the musculoskeletal system and limited effectiveness of opioid medication, psychosomatic comorbidities should be evaluated. Instead of continued and increased opioid medication, pain coping strategies and opioid withdrawal should be tested.

Analgesics, Opioid↗

Advances in the therapy of gastric cancer.

Many issues remain unclear in the management of gastric cancer. Randomized trials have failed to show the superiority of D2 over D1 dissection, and comparisons between countries showing higher survival rates following more extensive surgery may be influenced at least in part by the fact that D1 dissection underestimates disease stage in many patients. No studies have yet shown a benefit from adjuvant chemotherapy. However, the Southwest Oncology Group (SWOG) 9008 trial provides convincing evidence that a regimen of postoperative 5-fluorouracil (5-FU)-based chemoradiotherapy improves disease-free and overall survival when compared with observation alone. In the chemotherapy of advanced disease, use of the epirubicin plus cisplatin plus 5-FU (ECF) regimen leads to significantly longer median survival than 5-FU plus adriamycin plus methotrexate-C (FAMTX), but the rate of complete response remains low and the effect on longterm survival minimal. There are indications that neoadjuvant chemotherapy may increase the resectability of tumors and reduce risk of postoperative recurrence. Substantial improvements in outcome are likely to depend on the integration into multimodality strategies of novel, molecularly targeted agents in all stages of gastric cancer treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Hypothermic circulatory arrest with and without cold selective antegrade cerebral perfusion: impact on neurological recovery and tissue metabolism in an acute porcine model.

OBJECTIVE: Clinically, selective antegrade cerebral perfusion (SACP) seems to be associated with a better neurological outcome compared to hypothermic circulatory arrest (HCA) alone, but the pathophysiological mechanisms are not well understood. Therefore, this study was undertaken to assess the effects of HCA with and without SACP on the cerebral integrity using multimodal neurophysiological monitoring. METHODS: 12 pigs were randomly assigned to 100 min HCA at 20 degrees C brain temperature with (n = 6) and without (n = 6) SACP. Haemodynamics, metabolics and neurophysiology (EEG, SSEP, ICP, spectroscopy, cerebral tissue monitoring) were monitored. Animals were sacrified 4 h after reperfusion and the brains perfused for histopathological assessment. RESULTS: There were no clinically relevant differences in hemodynamics between groups. During reperfusion, EEG and SSEP recovery was significantly faster in the SACP group (P < 0.05). The rise in ICP during reperfusion was markedly reduced in the SACP group (P < 0.01) for the trend). Three hours after reperfusion, median ICP was 130% compared to baseline in the SACP group and 225% in the HCA group (P < 0.01). Invasive as well as noninvasive cerebral monitoring indirectly indicates the occurrence of tissue acidosis in the HCA group even 4 h after HCA. CONCLUSIONS: Cold SACP is associated with better neurophysiological recovery and less cerebral edema, indicated by lower intracranial pressures during reperfusion. Neurophysiological recovery correlated well with the rise in ICP. HCA alone causes prolonged acidosis in the brain tissue during reperfusion. From these data, SACP appears to be superior to HCA alone, but further studies have to elucidate the optimal regimes for SACP.

Animals↗

Feasibility of a novel deformable image registration technique to facilitate classification, targeting, and monitoring of tumor and normal tissue.

PURPOSE: To investigate the feasibility of a biomechanical-based deformable image registration technique for the integration of multimodality imaging, image guided treatment, and response monitoring. METHODS AND MATERIALS: A multiorgan deformable image registration technique based on finite element modeling (FEM) and surface projection alignment of selected regions of interest with biomechanical material and interface models has been developed. FEM also provides an inherent method for direct tracking specified regions through treatment and follow-up. RESULTS: The technique was demonstrated on 5 liver cancer patients. Differences of up to 1 cm of motion were seen between the diaphragm and the tumor center of mass after deformable image registration of exhale and inhale CT scans. Spatial differences of 5 mm or more were observed for up to 86% of the surface of the defined tumor after deformable image registration of the computed tomography (CT) and magnetic resonance images. Up to 6.8 mm of motion was observed for the tumor after deformable image registration of the CT and cone-beam CT scan after rigid registration of the liver. Deformable registration of the CT to the follow-up CT allowed a more accurate assessment of tumor response. CONCLUSIONS: This biomechanical-based deformable image registration technique incorporates classification, targeting, and monitoring of tumor and normal tissue using one methodology.

Biomechanical Phenomena↗

Hippocampus activity differentiates good from poor learners of a novel lexicon.

Language proficiency is a key to academic and workplace success for native and non-native speakers. It is largely unknown, however, why some people pick up languages more easily than others. We used event-related functional magnetic resonance imaging (e-fMRI) to elucidate which brain regions are modulated during the acquisition of a novel lexicon and which of these learning-related activity changes correlated with general semantic language knowledge. Fourteen healthy young subjects learned a novel vocabulary of 45 concrete nouns via an associative learning principle over the course of five blocks during e-fMRI. As a control condition, subjects took part in a structurally identical "No-Learning" condition lacking any learning principle. Overall, increasing vocabulary proficiency was associated with (intercorrelated) modulations of activity within the left hippocampus and the left fusiform gyrus, regions involved in the binding and integration of multimodal stimuli, and with an increasing activation of the left inferior parietal cortex, the presumed neural store of phonological associations. None of these activity changes were observed during the control condition. Furthermore, subjects who showed less suppression of hippocampal activity over learning blocks scored higher on semantic knowledge in their native language and learned the novel vocabulary more efficiently. Our findings indicate that (a) the successful acquisition of a new lexicon depends on correlated amplitude changes between the left hippocampus and neocortical regions and (b) learning-related hippocampus activity is a stable marker of individual differences in the ability to acquire and master vocabularies.

Adult↗

The space of senses: impaired crossmodal interactions in a patient with Balint syndrome after bilateral parietal damage.

Balint syndrome after bilateral parietal damage involves a severe disturbance of space representation including impaired oculomotor behaviour, optic ataxia, and simultanagnosia. Binding of object features into a unique spatial representation can also be impaired. We report a patient with bilateral parietal lesions and Balint syndrome, showing severe spatial deficits in several visual tasks predominantly affecting the left hemispace. In particular, we tested whether a loss of spatial representation would affect crossmodal interactions between simultaneous visual and tactile events occurring at the same versus different locations. A tactile discrimination task, where spatially congruent or incongruent visual cues were delivered near the patient's hands, was used. Following stimulation of the left hand in the left side of space, we observed visuo-tactile interactions that were not modulated by spatially congruent conditions. In contrast, performance following stimulation of the right hand in the right side of space was affected in a spatially selective manner--facilitated for congruent stimuli and slowed for incongruent stimuli. To dissociate effects on somatotopic and spatiotopic coordinates, we crossed the patient's hands during unimodal tactile discriminations. Tactile performance of the left hand improved when it was positioned in the right hemispace, whereas placing the right hand in left space produced no significant changes, suggesting that left-sided tactile inputs are coded with respect to a combination of limb- and trunk-centred coordinates. These data converge with recent findings in animals and healthy humans to indicate a critical role of the posterior parietal cortex in multimodal spatial integration, and in the fusion of different coordinates into a unified representation of space.

Analysis of Variance↗

Insular volumes in first-episode schizophrenia: gender effect.

Insula is a multimodal sensory integration region that acts as a gateway between somatosensory areas and limbic structures such as amygdala. Only a handful of region of interest (ROI) studies have suggested insular volume reduction in patients with schizophrenia but none have documented a gender effect on the volume of this structure. The authors used magnetic resonance images to measure insular volumes in previously untreated patients with first-episode schizophrenia (N=30) relative to those of healthy comparison subjects (N=30). Correlations with symptom severity were carried out. Intracranial volume was used as a covariate in the analysis. Female patients (N=15) had significantly reduced right insular volume relative to healthy female comparison subjects (p<0.05). On preliminary analysis, the right and left insular volumes in female patients had significant negative correlations with the positive symptoms scores (p<0.05), but not on correcting for multiple comparisons. Insula is developmentally and phylogenetically a watershed region where the more primitive allocortex transitions into the more developed isocortex. Thus its role as a substrate of neurodevelopmental hypothesis in schizophrenia and the interplay with gender deserves more attention.

Adult↗

Development of configural 3D object recognition.

There is evidence for the late development in humans of configural face and animal recognition. We show that the recognition of artificial three-dimensional (3D) objects from part configurations develops similarly late. We also demonstrate that the cross-modal integration of object information reinforces the development of configural recognition more than the intra-modal integration does. Multimodal object representations in the brain may therefore play a role in configural object recognition.

Adolescent↗

Computer-based imaging and interventional MRI: applications for neurosurgery.

Advances in computer technology and the development of open MRI systems definitely enhanced intraoperative image-guidance in neurosurgery. Based upon the integration of previously acquired and processed 3D information and the corresponding anatomy of the patient, this requires computerized image-processing methods (segmentation, registration, and display) and fast image integration techniques. Open MR systems equipped with instrument tracking systems, provide an interactive environment in which biopsies and minimally invasive interventions or open surgeries can be performed. Enhanced by the integration of multimodal imaging these techniques significantly improve the available treatment options and can change the prognosis for patients with surgically treatable diseases.

Biopsy↗

CT of thoracic aortic disease.

The role of CT continuous to expand. However, competing modalities and their value and limitations for the same clinical indication should also be understood. In addition, CT radiation patient dose must be justified in the context of adding diagnostic value. Techniques for quantitative CT and their utility for specific applications are important, and protocols must be tailored to answer the clinical need. Finally, newer post-processing techniques, including surface rendering, maximum intensity projections (MIP), 3-D displays and multimodality image integration can certainly be helpful for diagnosis and usually they improve the referring clinicians' comprehension, however these methods may not necessarily provide additional diagnostic information.

Aorta, Thoracic↗

Epidermal growth factor receptor inhibitors in lung cancer therapy.

Over the past decade our evolving knowledge and understanding of cancer biology has allowed rapid progression in the development of targeted cancer therapy. Improving lung cancer mortality has remained a difficult task; however, therapeutic agents directed against the epidermal growth factor receptor (EGFR) have provided physicians with a valuable new tool to integrate into multimodality therapy. EGFR inhibitors have been shown to elicit meaningful antitumor effects and quality-of-life benefits with acceptable toxicity. The rationale, utility, toxicity profile, and therapeutic strategy of EGFR-targeted therapy will be reviewed.

Journal Article↗

Association of efferent neurons to the compartmental architecture of the superior colliculus.

The superior colliculus is a layered structure in the mammalian midbrain serving multimodal sensorimotor integration. Its intermediate layers are characterized by a compartmental architecture. These compartments are apparent through the clustering of terminals of major collicular afferents, which in many instances match the heterogeneous distribution of tissue components such as acetylcholinesterase, choline acetyltransferase, substance P, and parvalbumin. The present study was undertaken to determine whether efferent cells observe this compartmental architecture. It was found that subpopulations of both descending and ascending collicular efferents originate from perikarya situated in characteristic positions relative to the collicular compartments defined by elevated acetylcholinesterase activity and that their dendrites appear to be specifically coordinated with the heterogeneous environment. With the specific interlocking of afferent and efferent neurons through spatially distinguished neural networks, the compartmental architecture apparently constitutes an essential element for the determination of information flow in the superior colliculus.

Acetylcholinesterase↗