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Multimodality therapy in the treatment of lung cancer.

Lung cancer is the leading cause of cancer death in the world, causing more than one million deaths each year. The incidence and mortality rates are highest in the United States and Europe and continue to increase in developing nations. Non-small cell lung cancer (NSCLC) accounts for 80 to 85% of all new cases of lung cancer. The majority of patients with NSCLC present with advanced disease at the time of diagnosis. Although the prognosis of advanced NSCLC is very poor, current chemotherapy combinations have been shown to improve 1-year survival and quality of life for these patients. Approximately one third of patients with NSCLC are diagnosed with locally advanced disease. Although cure rates are modest and variable in locally advanced NSCLC, multimodality therapy (chemotherapy in combination with surgery or radiotherapy) has resulted in statistically significant improvement in 5-year survival when compared with surgery or radiotherapy alone. Patients with early-stage NSCLC have the best long-term survival rates following surgical resection; however, systemic recurrences remain a problem in the majority of these patients. The rationale for treating patients with early-stage NSCLC with combined-modality therapy (chemotherapy and surgery) is compelling, and several randomized trials are currently in progress. Although progress has been slow, when we consider the recent advances in smoking prevention, smoking cessation, staging classification, imaging and diagnostic techniques, screening and therapeutic modalities, and multidisciplinary care, as well as in the understanding of the molecular pathogenesis of lung cancer, the future, in my opinion, is very promising.

Journal Article↗

Multimodality treatment of neuroendocrine tumors of the thymus.

BACKGROUND: Neuroendocrine tumors of the thymus are rare neoplasms. Four patients with this tumor who underwent multimodality treatment are presented and the literature is briefly reviewed. METHODS: The medical records of all patients treated for neuroendocrine tumors of the thymus from 1979 to 2002 were reviewed. Tumors were classified using a slight modification of the World Health Organization criteria. RESULTS: The patients' median age was 38 years. All patients underwent extensive excision of the tumor. Histological diagnosis was atypical carcinoid (2), typical carcinoid (1), and small cell carcinoma (1). All patients developed recurrence(s). One patient died 132 months after diagnosis. The remaining three patients are alive with no symptoms at 135, 99, and 35 months, respectively, after diagnosis. Two patients with recurrences have been on treatment with Octreotide LAR with satisfactory results. One patient is free of disease. CONCLUSIONS: Neuroendocrine tumors of the thymus are potentially aggressive tumors. Radical resection is the treatment of choice. The encouraging results obtained by administration of Octreotide LAR in two of our patients warrant further investigation.

Adult↗

Multimodality aesthetic skin rejuvenation.

Patients requesting skin correction and rejuvenation are motivated by a number of clinical problems. Photo damage, abnormal pigmentation or vascularity, textural problems, rhytides, and laxity due to chronological aging are the primary complaints of the majority of patients. Advances in new technology in the past decade have provided the skin correction specialist with new options for treatment. Specialists with multiple technology options then face a new dilemma. What is the best treatment plan for individual patients when many options exist? Over the past five years we have developed an approach to our patients based on an individualized treatment plan consisting of a prescribed series of skin correction treatments utilizing the most specific rejuvenation techniques for each clinical problem. Multimodality aesthetic skin rejuvenation (MMASR) emphasizes the corrective process and utilization of the most appropriate technology for the patient's clinical skin problem as evidenced by the clinical examination. MMASR also takes into consideration patient bias, cost concerns, expectations of treatment, and feasibility of combining different technologies in the same treatment session. Combining skin rejuvenation techniques with surgical rejuvenation is also reviewed as an option for patients with both facial laxity and clinical skin problems.

Acne Vulgaris↗

Multimodal treatment of osteosarcoma lung metastases.

OBJECTIVE: The diagnostic procedures, role of surgery and multimodal treatment for osteosarcoma pulmonary metastases are examined. METHODS: From January 2000 to June 2005, we observed 35 patients with osteogenic repetitions. Patients were studied by total-body computerised tomography (CT) and by thoracic single-photon emission computerised tomography (SPECT). Preoperative histological diagnosis was obtained by CT-guided transthoracic needle biopsy (23 cases) and fibre-optic bronchoscopy (12 cases). RESULTS: Four lower, 6 upper and 2 middle lobectomies were carried out using a thoracotomy approach. Video-assisted thoracoscopy was used in the other 23 patients who underwent 36 wedge resections. CT showed a sensitivity of 86 % and a specificity of 66 %; SPECT had a sensitivity of 80 % and a specificity of 100 %. Twenty-five patients are still living 25 +/- 11 months after the intervention. CONCLUSIONS: SPECT was demonstrated to offer a better result in the individualisation of secondary pulmonary nodules after primary osteosarcoma. The excision of all resectable lung metastases, integrated in a multidisciplinary strategy, offers good results in terms of survival.

Adult↗

[Multimodal carotid occlusion test for determining risk of infarct before therapeutic internal carotid artery occlusion].

UNLABELLED: In patients with head and neck carcinoma and extensive cervical metastasis, the topographic and functional relationship of the tumor to the carotid artery is highly important. In case of suspected carotid infiltration, the possibility of a carotid resection or a prosthetic replacement has to be considered preoperatively. Treatment of cavernous carotid aneurysms may also require sacrificing the internal carotid artery (ICA). An interdisciplinary test occlusion of the ICA was performed to assess cerebral collateral circulation prior to permanent carotid occlusion. MATERIALS AND METHODS: Fifty-two patients with cervical tumors (n = 45) or inoperable aneurysms (n = 7) were examined. The endovascular balloon test occlusion (BTO) of the ICA was combined with monitoring of the neurological status, cardiovascular status (EKG, blood pressure), cortical function (EEG), and single photon emission CT (SPECT) imaging of the regional cerebral blood flow (rCBF) with 99mTechnetium-HMPAO. In the last 24 patients, transcranial Doppler sonography (TCD) of the ipsilateral middle cerebral artery (MCA) was added for direct hemodynamic monitoring during BTO. In order to improve the diagnostic value of the test results and to simulate hemodynamic crisis, the cerebrovascular reserve capacity was then evaluated with acetazolamide (Diamox). RESULTS: BTO could be performed without neurological complications or carotid dissection. In eight (15%) patients BTO had to be interrupted previously due to neurological symptoms or a delta-EEG. These patients and patients with highly pathological test results in SPECT imaging (n = 9) or TCD (n = 3) were excluded from permanent carotid occlusion. Ten (19%) patients were definitely occluded without hemodynamic complications, but two patients suffered embolic infarctions, which can not be predicted by this procedure. In two patients with a severe hypoperfusion in SPECT imaging, the ICA had to be ligated under emergency conditions following a carotid rupture. Predictably, a hemodynamic infarction occurred postoperatively in both patients. CONCLUSIONS: The multimodal BTO with brain perfusion imaging (HMPAO-SPECT) and quantitative blood flow monitoring (TCD) allows a hemodynamic stroke risk assessment prior to permanent occlusion of the ICA. The procedure is important for planning of the therapeutic strategy and for the preoperative dialogue with the patient. Embolic ischemic complications can not be predicted.

Adult↗

Multimodality evoked potentials in children with moyamoya disease.

Twenty Japanese children with Moyamoya disease were investigated by examining the multimodality evoked potentials (BAEPs, FVEPs and SSEPs). BAEPs were abnormally prolonged wave I-III and wave III-V in each one (10%). FVEPs were abnormal in 6 (30%), included prolonged latencies, reduced amplitudes and poor waveform in one each, and delayed latencies as well as reduced amplitudes in three. FVEPs significantly correlated with intellectual deterioration (p less than 0.01). SSEPs were abnormal in 13 (65%) significantly more frequent than BAEPs and FVEPs (p less than 0.01); reduction of N20 in 7, delayed latencies of N13-N20 in 4, and both delayed latencies and reduced amplitudes of N20 in two. These findings correlated well with the neurologic deficits, CT findings and EEG findings in this progressive cerebrovascular disease (Moyamoya disease) in children.

Adolescent↗

A second quantization formulation of multimode dynamics.

A new formalism for calculating and analyzing many-mode quantum dynamics is presented. The formalism is similar in spirit to the second quantization formulation of electronic structure theory. The similarity means that similar techniques can be employed for calculating the many-mode nuclear wave function. As a consequence a new formulation of the vibrational self-consistent-field (VSCF) method can be developed. Another result is that the formalism opens up for the construction of new methods that go beyond the VSCF level. A vibrational coupled cluster (VCC) theory is constructed using the new formalism. The size-extensivity concept is introduced in the context of multimode wave functions and the size extensivity of approximate VCC methods is illustrated in comparison with the non-size-extensive vibrational configuration interaction method.

Journal Article↗

Chaos in a multimode solid-state laser system.

When a nonlinear crystal is placed within a multimode solid-state laser cavity, deterministic fluctuations are induced in the output intensity. In this paper, the results of our studies of the intensity noise in a diode pumped, intracavity frequency doubled Nd:YAG (neodymium doped yttrium aluminum garnet) laser will be presented. First, a novel technique to eliminate these fluctuations is described. Second, the observation of antiphase states in the laser output is discussed. These states are characterized by a cyclic periodic pulsing of the individual longitudinal mode intensities. Finally, the statistical properties of chaotic intensity fluctuations are characterized. It is be demonstrated that it is possible to accurately model the laser dynamics by a system of globally coupled, nonlinear oscillators.

Journal Article↗

A multimode analysis of the gas-phase photoelectron spectra in oligoacenes.

We present a multimode vibrational analysis of the gas-phase ultraviolet photoelectron spectra of the first ionization in anthracene, tetracene, and pentacene, using electron-vibration constants computed at the density functional theory level. The first ionization of each molecule exhibits a high-frequency vibronic structure; it is shown that this regularly spaced feature is actually the consequence of the collective action of several vibrational modes rather than the result of the interaction with a single mode. We interpret this feature in terms of the missing mode effect. We also discuss the vibronic coupling constants and relaxation energies obtained from the fit of the photoelectron spectra with the linear vibronic model.

Anthracenes↗

Multipole-multimode Floquet theory in nuclear magnetic resonance.

In this paper, we present a new analytical approach for describing the spin dynamics of synchronous and asynchronous time-dependent modulations in solid-state nuclear magnetic resonance experiments. The approach, based on multimode Floquet theory, employs the multipole operator basis of Sanctuary for spin description and illustrates the time evolution in the Floquet-Liouville space using the effective Hamiltonians obtained from the contact (or van Vleck) transformation procedure. Since the Hamiltonian and the density operator are expressed in terms of irreducible tensor operators, extensions to higher spin magnitudes (I>12) and multiple spins are quite straightforward and permit analytical treatments for many problems. We outline the general underlying principles involved in this approach with a brief mention of its potential application in other branches of spectroscopy.

Algorithms↗

Theory of heteronuclear decoupling in solid-state nuclear magnetic resonance using multipole-multimode Floquet theory.

A formal theory for heteronuclear decoupling in solid-state magic angle spinning (MAS) nuclear magnetic resonance experiments is presented as a first application of multipole-multimode Floquet theory. The method permits a straightforward construction of the multispin basis and describes the spin dynamics via effective Floquet Hamiltonians obtained using the van Vleck transformation method in the Floquet-Liouville space. As a test case, we consider a model three-spin system (I2S) under asynchronous time modulations (both MAS and rf irradiation) and derive effective Hamiltonians for describing the spin dynamics in the Floquet-Liouville space during heteronuclear decoupling. Furthermore, we describe and evaluate the origin of cross terms between the various anisotropic interactions and illustrate their exact contributions to the spin dynamics. The theory presented herein should be applicable to the design and understanding of pulse sequences for heteronuclear and homonuclear recoupling and decoupling.

Algorithms↗

Remarkable impact of intermode couplings on multimode vibronic dynamics: the photoelectron spectrum of CH3F.

Electronic and nuclear motions on intersecting potential energy surfaces are often intricately mixed and the spectrum can become very complex. Here we choose the strongly coupled Jahn-Teller system CH3F+ as a prototype example, and establish the importance of intermode coupling terms on multimode vibronic dynamics. The theoretical approach consists of a full second-order diabatic vibronic Hamiltonian, constructed from high-quality electronic structure calculations. Our results compare amazingly well with the experimental data. This highlights the success of the present theoretical approach in explaining the complex structure of vibronic spectra, ubiquitous in molecular systems.

Journal Article↗

Multimode wavelet basis calculations via the molecular self-consistent-field plus configuration-interaction method.

Wavelets provide potentially useful quantum bases for coupled anharmonic vibrational modes in polyatomic molecules as well as many other problems. A single compact support wavelet family provides a flexible basis with properties of orthogonality, localization, customizable resolution, and systematic improvability for general types of one-dimensional and separable systems. While direct product wavelet bases can be used in coupled multidimensional problems, exponential scaling of basis size with dimensionality ultimately provides limits on the number of coupled modes that can be treated simultaneously in exact quantum calculations. The molecular self-consistent-field plus configuration-interaction method is used here in multimode wavelet calculations to reduce the basis size without sacrificing flexibility or the ability to systematically control errors. Both two-dimensional Cartesian coordinate and three-dimensional curvilinear coordinate systems are examined with wavelets serving as universal bases in each case. The first example uses standard Daubechies [Ten Lectures on Wavelets (SIAM, Philadelphia (1992)] wavelets for each mode and the second adapts symmlet wavelets to intervals for each of the curvilinear coordinates.

Journal Article↗

Multipole-multimode Floquet theory of rotational resonance width experiments: 13C-13C distance measurements in uniformly labeled solids.

A formal description of zero-quantum (ZQ) NMR processes using multipole-multimode Floquet theory is proposed for studying polarization transfer in magic angle spinning experiments. Specifically, we investigate the factors affecting the accuracy and precision of 13C-13C distance measurements that are based on ZQ-magnetization exchange processes in rotational resonance width experiments. With suitable examples drawn from measurements in N-acetyl-[U-13C,15N]-L-valine-L-leucine, we substantiate our approach and propose methods for improving the accuracy and reliability of such 13C-13C distance measurements in uniformly 13C, 15N-labeled solids. In addition, the theoretical model presented in this article provides a more general framework for describing relaxation phenomena involving multiple decay rate constants in zero-quantum processes.

Carbon Isotopes↗

Description of depolarization effects in double-quantum solid state nuclear magnetic resonance experiments using multipole-multimode Floquet theory.

Using an analytical model based on multipole-multimode Floquet theory (MMFT), we describe the polarization loss (or depolarization) observed in double-quantum (DQ) dipolar recoupling magic angle spinning (MAS) experiments. Specifically, the factors responsible for depolarization are analyzed in terms of higher order corrections to the spin Hamiltonian in addition to the usual phenomenological decay rate constant. From the MMFT model and the effective Hamiltonians, we elucidate the rationale behind the inclusion of a phenomenological damping term in DQ recoupling experiments. As a test of this theoretical approach, the recoupling efficiency of one class of (13)C-(13)C and (13)C-(15)N resonance width dipolar recoupling experiments are investigated at different magnetic field strengths and compared with the more exact numerical simulations. In contrast to existing analytical treatments, the role of higher order corrections is clearly explained in the context of the MMFT approach leading to a better understanding of the underlying spin physics. Furthermore, the analytical model presented herein provides a general framework for describing coherent and incoherent effects in homonuclear and heteronuclear DQ MAS recoupling experiments.

Algorithms↗

Potential energy surface and MULTIMODE vibrational analysis of C2H3+.

A full dimensional, ab initio-based semiglobal potential energy surface for C(2)H(3) (+) is reported. The ab initio electronic energies for this molecule are calculated using the spin-restricted, coupled cluster method restricted to single and double excitations with triples corrections [RCCSD(T)]. The RCCSD(T) method is used with the correlation-consistent polarized valence triple-zeta basis augmented with diffuse functions (aug-cc-pVTZ). The ab initio potential energy surface is represented by a many-body (cluster) expansion, each term of which uses functions that are fully invariant under permutations of like nuclei. The fitted potential energy surface is validated by comparing normal mode frequencies at the global minimum and secondary minimum with previous and new direct ab initio frequencies. The potential surface is used in vibrational analysis using the "single-reference" and "reaction-path" versions of the code MULTIMODE.

Journal Article↗

Multimodality reperfusion therapy for acute myocardial infarction.

With the strong and direct relation between early reperfusion in acute myocardial infarction (AMI) and improved clinical outcomes, attention has focused on new means of improving rates of reperfusion and accelerating every stage of AMI evaluation and management, from the onset of symptoms of myocardial infarction to the achievement of reperfusion. Critical pathways to streamline the evaluation and management of AMI have cut minutes and even hours off in-hospital treatment times for patients with AMI; public health initiatives focus on educational efforts to shorten time to hospital arrival. The latest advance in fibrinolytic therapy is the availability of bolus fibrinolytic agents with safety and efficacy in large phase III trials comparable to accelerated intravenous infusion regimens. Faster and simpler fibrinolytic regimens may shorten door-to-needle time, reduce medication errors, and facilitate prehospital thrombolysis. Bolus fibrinolytic agents are being evaluated for use in combination with other interventions to open occluded coronary arteries, including acute percutaneous coronary intervention, the glycoprotein IIb/IIIa platelet inhibitors, or both. The goal of this "multimodality" approach to AMI management is to minimize time to reperfusion and maximize the percentage of patients who achieve complete arterial patency and myocardial perfusion without bleeding complications.

Critical Pathways↗

Survival after multimodality treatment for stage IIIC endometrial cancer.

OBJECTIVE: Our purpose was to review our results of multimodality treatment of lymph node metastasis in endometrial cancer (stage IIIC). STUDY DESIGN: All patients underwent surgical staging for endometrial cancer with complete pelvic and aortic lymphadenectomy. All macroscopic nodal metastases were resected. Patients with microscopic nodal metastasis received adjuvant teletherapy, whereas those with macroscopic nodal metastasis received chemotherapy (carboplatin AUC 5 and paclitaxel 135 mg/m2 every 3 weeks for 6 courses) followed by teletherapy. RESULTS: Twenty-one patients had stage IIIC disease, and one had stage IVB (inguinal nodal metastasis). Sixty-four percent of tumors were poorly differentiated. Fifty-five percent of patients had pelvic nodal metastasis only and 41% had macroscopic nodal metastasis. At a median follow-up of 3.8 years, 32% of patients had recurrence, all extrapelvic. Overall mean survival was 48 months and progression-free survival was 40 months. Overall survival for microscopic nodal metastasis was >60 months versus 35 months for macroscopic metastasis. Overall survival for pelvic nodal metastasis was 53 months versus 42 months for aorticinguinal metastasis. There were no complications from lymphadenectomy, a 22% chemotherapeutic toxicity, and a 14% radiation toxicity. CONCLUSION: Our surgical, chemotherapeutic, and radiation treatment protocol for stage IIIC endometrial cancer produced minimal toxicity and good survival.

Adult↗