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PubMed2005

Copper(II) chloride complexes with multimodal ligands based on the cyclotriphosphazene platform.

The reaction of hexakis(2-pyridyloxy)cyclotriphosphazene (L) and hexakis(4-methyl-2-pyridyloxy)cyclotriphosphazene (MeL) with copper(ii) chloride afford the complexes [CuLCl(2)], [(CuCl(2))(2)(MeL)], [CuLCl]PF(6) and [Cu(MeL)Cl]PF(6). The single-crystal X-ray structure of [CuLCl(2)] shows the copper ion to be in a square based pyramidal distorted trigonal bipyramidal (SBPDTBP) environment (tau= 0.47) with L acting as a kappa(3)N donor, coordinating via the nitrogen atoms from two non-geminal pyridyloxy pendant arms, a nitrogen atom in the phosphazene ring and two chloride ions. In the dimetallic complex, [(CuCl(2))(2)(MeL)], the geometry about both (symmetry related) copper(ii) centres is also SBPDTBP (tau= 0.57) with a 'N(3)Cl(2)' donor set. In the monocation of [CuLCl]PF(6), L acts as a kappa(5)N donor, bonding to the copper(ii) centre through the nitrogen atoms of four pyridyloxy pendant arms, a phosphazene ring nitrogen atom and a chloride ion to give an elongated rhombic octahedral coordination sphere. The phosphazene ring atoms remain virtually coplanar in all three structures as a consequence of the phenoxy-hinge, which links the pyridine pendant donors to the cyclotriphosphazene platform, allowing the formation of six-membered chelate rings. The spectroscopic (mass spectral, EPR and electronic) and magnetic properties of the complexes are discussed. The EPR and variable temperature magnetic susceptibility results for the dicopper complex, [(CuCl(2))(2)(MeL)], point to a very weak electronic interaction between the metal atoms.

Journal Article↗
PubMed2001

Effect of multimodality therapy on circulating vascular endothelial growth factor levels in patients with oesophageal cancer.

BACKGROUND: Angiogenesis is critical for tumour growth and metastasis. The switch to the angiogenic phenotype depends on the net balance between positive and negative angiogenic factors released by the tumour. It was hypothesized that patients with oesophageal cancer would express raised serum levels of vascular endothelial growth factor (VEGF) which would return to normal values with neoadjuvant chemoradiotherapy. METHODS: Forty-four patients with oesophageal cancer who were selected for treatment with neoadjuvant chemoradiotherapy had blood samples taken before treatment, during chemoradiotherapy, before operation, on days 1, 3 and 5 after surgery, and 3 months after resection. Serum levels of VEGF were measured. Values were correlated with response to treatment. Controls were patients who were undergoing surgery for non-malignant conditions. RESULTS: Serum VEGF levels were raised in patients with oesophageal cancer compared with age-matched controls (mean 247 versus 1157 pg/ml; P < 0.01). VEGF levels were unaffected by neoadjuvant treatment but fell significantly on the first day after operation (652 versus 1057 pg/ml before operation; P < 0.05). No decrease occurred in control patients. VEGF levels had returned to preoperative levels by day 5. A similar postoperative rise in VEGF levels was seen in the control subjects (1194 pg/ml on day 5 versus 71 pg/ml before operation; P = 0.001). There was no correlation between VEGF level and response to treatment or tumour stage. VEGF levels had decreased significantly at 3 months following tumour resection (594 versus 1558 pg/ml on day 5; P = 0.03). CONCLUSION: VEGF levels are raised in patients with oesophageal cancer and are unaltered by neoadjuvant treatment, suggesting an additional source other than tumour cells for this proangiogenic agent.

Adenocarcinoma↗
PubMed2000

Multimodal event-related potential P3 after transient global amnesia.

The putative generators of the event-related P3 component are still a matter of debate. There is reasonable evidence that the mesial temporal lobe structures are crucial in the generation of event-related potentials. Transient global amnesia (TGA) is characterized by anterograde and retrograde amnesia without neurological deficits in which a temporal hypoperfusion is the most likely pathomechanism. The aim of this study is to evaluate a possible delay in the P3 latency in a cohort of patients with TGA (n = 18). We used classic oddball paradigms with visual and auditory stimuli. The P3 latencies were compared to 18 age-matched patients with transient ischaemic attacks (TIAs) in the carotid artery territory and 23 age-matched controls. The mean age of the patients was 60.1 years (SD 14.1), in the TIA group 64.7 (SD 12.1) and 57.7 (SD 10.1) in the controls; the mean time interval between onset of TGA symptoms and performance of P3 investigations was 4.3 days (range 1-7 days); and the mean latencies measured at the vertex (Cz electrode) were 422.9 ms (SD 44.6) for the TGA patients, 436.4 ms (SD 62.1) for the TIA group, and 409.3 ms (SD 48.5) for the controls in the visual paradigm and 371.7 ms (SD 41.7), 399.7 ms (SD 51.2) and 385.3 ms (SD 46.5) in the auditory paradigm for the TGA, the TIA and the control groups. The P-values were not significant. These results suggest different neuronal networks in the generation of scalp P3 from those responsible for the disturbance of episodic memory in TGA.

Acoustic Stimulation↗
PubMed2001

Multimodal P3 under different attentional states in mesial temporal lobe epilepsy.

BACKGROUND: Several studies demonstrate that the P3 component of the event-related potentials (ERP) is generated by mesial temporal structures. The P3 is considered as endogenous information processing component independent from modality. PURPOSE: The aim of this investigation was to study whether the P3 latency elicited by auditory and visual stimuli under different attentional states is influenced by the mesial temporal lobe epilepsy (mTLE). METHODS: The event related P3 component of 10 right handed patients (7 m/3 f, mean age 31.3 years (SD 7.3), median 31.5, range 20-47) with unilateral mTLE were studied and compared with 10 age matched controls (5 m/5 f, mean age 36.6 years (SD 12.6), median 32.1, range 22-48). Diagnosis of mTLE was based on seizure description, clinical history and examination, prolonged video-EEG monitoring, magnetic resonance imaging (MRI), interictal and ictal SPECT. P3 potentials were elicited with a visual and auditory three stimulus discrimination paradigm. RESULTS: The latency of the P3 response to the auditory stimulus under automatic and effortful attention was delayed (423.3 ms (SD 60.4) and 436.9 ms (SD 83.4)) compared with a control group (359 ms (SD 42.4) and 354.2 ms (SD 39.7); P = 0.039 and P = 0.012, ANOVA), while the P3 latencies to visual stimuli under both tested attentional states (407.3 ms (SD 52.9) and 390.6 ms (SD 40.2)) did not differ from controls (378.2 ms (SD 48.6) and 378.2 ms (SD 55.4)). P3 latencies to auditory novel paradigm in patients with right sided mTLE, but not left sided mTLE, differed significantly from controls (P = 0.01). CONCLUSION: The results suggest a modality dependence of the P3 component in patients with mTLE. The novelty processing of auditory stimuli is disturbed in patients with right sided mTLE.

Adult↗
PubMedDate not supplied

A multimodality approach to the diagnosis of breast hamartomas with atypical mammographic appearance.

The ultrasonographic appearance of breast hamartomas (BHs) is described and its diagnostic utility is discussed in this study of 27 women with mammographic findings both typical and atypical of BH. The role of computed tomography (CT) in the diagnosis of BH of atypical mammographic appearance is also analyzed. These 27 cases of BH were detected in women submitted to mammographic screening. Ages ranged from 45 to 65 years (mean age 52.6 years). In all cases physical and ultrasonographic examinations were carried out. CT studies were carried out in seven cases. Core biopsy was performed in 18 cases of lesions with a mammographic appearance atypical of BH. Lesions were palpable in 9 cases and nonpalpable in 18. Mammographic appearance was characteristic in nine cases. In 19 cases a hypoechoic solid mass with hyperechoic lines and/or bands was seen. This ultrasonographic image is suspicious of BH. Finally, both CT and core biopsy findings were of great help in the diagnosis of BH in the cases where mammographic and ultrasonographic studies were inconclusive. We consider that a combination of mammography, ultrasonography, CT, and core biopsy is fundamental for the successful diagnosis of breast hamartomas not seen in typical form in mammograms.

Aged↗
PubMed2002

Digital photography and 3D MRI-based multimodal imaging for individualized planning of resective neocortical epilepsy surgery.

PURPOSE: Invasive presurgical work up of pharmacoresistant epilepsies presumes integration of multiple diagnostic modalities into a comprehensive picture of seizure onset and eloquent brain areas. During resection, reliable transfer of evaluation results to the patient's individual anatomy must be made. We investigated the value of digital photography-based grid localization in combination with preoperative three-dimensional (3D) magnetic resonance imaging (MRI) for clinical routine. METHODS: Digital photographs of the exposed cortex were taken before and after grid placement. Location of electrode contacts on the cortex was identified and schematically indicated on native cortex prints. Accordingly, transfer of contact positions to a 3D MRI brain-surface rendering was carried out manually by using the rendering software. Results of the electrophysiologic evaluation were transferred to either electrode contact reproduction and co-registered with imaging-based techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and functional MRI (fMRI). RESULTS: Digital photography allows precise and highly realistic documentation of electrode contact positions on the individual neocortical surface. Lesions underneath grids can be highlighted by semitransparent MRI surface rendering, and lobar boundaries can be identified. Because of integrating electrode contact positions into the postprocessed 3D MRI data set, imaging-based techniques can be codisplayed with the results of the electrophysiologic evaluation. Comparison with CT/MRI co-registration showed good accuracy of the method. However, grids not sewn to the dura at implantation can become subject to significant displacement. CONCLUSIONS: Digital photography in combination with preimplantation 3D MRI allows the generation of reliable tailored resection plans in neocortical epilepsy surgery. The method enhances surgical safety and confidence.

Adolescent↗
PubMed1988

Multimodal control of pituitary gonadotropin biosynthesis. Effects of gonadal steroids, GnRH, cyclic AMP and diacylglycerols.

We and others have previously shown that in the rat and the sheep gonadectomy increases the translational capacity of mRNAs encoding gonadotropin subunits alpha, LH beta and FSH beta. Injection of estradiol or of testosterone or dihydrotestosterone depresses the translational capacity of the mRNAs. After using estradiol to induce progesterone receptors in the pituitary of castrated animals, it was determined that progesterone does enhance the inhibitory effect of estradiol. We have also observed this inhibitory effect of gonadal steroids in vitro, suggesting that at least part of the steroid action is exerted at the pituitary level. Hybridization assay (Northern blot) using oligodeoxynucleotide probes complementary to a short portion in the cDNA strand of each subunit, showed gonadal steroids to act by decreasing the number of copies of mRNAs encoding LH and FSH subunits. Using anterior pituitary cells in culture, incubated in the presence of labeled methionine, we have confirmed our previous observation that GnRH stimulates the biosynthesis of the polypeptide chains of LH. This effect is not secondary due to LH release. It is not inhibited when incubation is performed in the presence of tunicamycin, an inhibitor of glycosylation. SDS-polyacrylamide gel electrophoresis of specific immunoprecipitates of polypeptides immunologically related to alpha allowed us to identify 3 forms of alpha-polypeptide differing in their apparent Mr:21K (partially glycosylated), 23K (authentic) and 25K (hyperglycosylated). Besides its stimulatory effect on the release and synthesis of LH, GnRH also stimulated the release of the 23K and 25K forms of alpha. In the presence of tunicamycin an additional 16K form of apoprotein-alpha was detected which accumulated within the cells. A cAMP analogue (8-Br-cAMP), intracellular cAMP generators (choleragen, forskolin), as well as an analogue of diacylglycerols (TPA) mimic the stimulatory action of GnRH. However, although no evidence has been obtained at present that either cAMP or diacylglycerols mediate the GnRH effect on the biosynthesis of the polypeptide chains of LH, our data suggest that phosphorylation of intracellular phosphoproteins plays a major role in this process.

Animals↗
PubMed2000

Multimodality treatment for patients with hepatocellular carcinoma: a single institution retrospective series.

BACKGROUND: The main therapeutic options for hepatocellular carcinoma (HCC) are hepatic resection, transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT) and regional chemotherapy (RC). METHODS: This study retrospectively examined the results of primary treatment of 600 patients with hepatocellular carcinoma selected according to the treatment guidelines of our facility and the results of various combination therapies for recurrent cases. The selection criteria of therapeutic options included the number and size of tumours and hepatic function. RESULTS: The selected primary treatment was hepatic resection for 53.7% of the cases, TAE for 31.5%, PEIT for 8.2% and RC for 6.6%,. The treatment for post-resection recurrence was TAE alone for 62.4% of the cases, TAE + RC for 4.0%, PEIT for 15.2%, TAE + PEIT alone for 4.8%, RC for 8.0% and hepatic resection for 5.6%. The treatment for post-TAE recurrence was TAE alone for 83% of the cases, TAE + PEIT for 9%, TAE + RC for 3%, RC alone for 3% and PEIT alone for 2%. For post-PEIT, therapy was PEIT alone for 71.4% of the cases and PEIT + TAE for 28.6%. For post-RC, RC alone was used for 92.5% and RC + PEIT for 7.5%. The cumulative 3 and 5-year survival rates were 84.4% and 70.6%, respectively for stage I; 61.5% and 48.6% for stage II; 52.7% and 20.5% for stage III; and 22.8% and 17.1% for stage IVA. The cumulative 5 and 7-year survival rates after the primary treatments were 52.% and 40.1%, respectively, for hepatic resection; 46.5% and 38.7%, for TAE; 49.6% and 33.1% for PEIT; and 16.7% and 8.3% for RC. CONCLUSIONS: To improve the treatment results for HCC, early detection is essential and various modalities of treatments in combination should be used for recurrence after primary treatment.

Adult↗
PubMed2003

Results of clinical trials of multimodality therapy for resectable nonsmall-cell lung cancer.

More than 50% of patients presenting with so-called early stage or surgical disease nonsmall-cell lung cancer will die of their cancer despite resection. Over the years, postoperative efforts to improve the survival of these patients have been disappointing. There is presently a lot of enthusiasm surrounding the strategy of preoperative or induction chemotherapy in the treatment of such patients. Worldwide, at least 4 large-scale ongoing cooperative group trials are evaluating this question at the present time. Only by completing these trials in a timely manner will we know if induction chemotherapy should become the standard of care for all patients with surgical disease nonsmall-cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗